Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
The transfer of mammalian embryos from an in vivo or in vitro environment to a suitable host to improve pregnancy or gestational outcome in human or animal. In human fertility treatment programs, preimplantation embryos ranging from the 4-cell stage to the blastocyst stage are transferred to the uterine cavity between 3-5 days after FERTILIZATION IN VITRO.
The naturally occurring transmission of genetic information between organisms, related or unrelated, circumventing parent-to-offspring transmission. Horizontal gene transfer may occur via a variety of naturally occurring processes such as GENETIC CONJUGATION; GENETIC TRANSDUCTION; and TRANSFECTION. It may result in a change of the recipient organism's genetic composition (TRANSFORMATION, GENETIC).
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
An encapsulated lymphatic organ through which venous blood filters.
Change in learning in one situation due to prior learning in another situation. The transfer can be positive (with second learning improved by first) or negative (where the reverse holds).
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Interfacility or intrahospital transfer of patients. Intrahospital transfer is usually to obtain a specific kind of care and interfacility transfer is usually for economic reasons as well as for the type of care provided.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
A ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Methods of implanting a CELL NUCLEUS from a donor cell into an enucleated acceptor cell.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Surgical procedure by which a tendon is incised at its insertion and placed at an anatomical site distant from the original insertion. The tendon remains attached at the point of origin and takes over the function of a muscle inactivated by trauma or disease.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
The rate dynamics in chemical or physical systems.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
Elements of limited time intervals, contributing to particular results or situations.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Substances that are recognized by the immune system and induce an immune reaction.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Established cell cultures that have the potential to propagate indefinitely.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Surgical reinnervation of a denervated peripheral target using a healthy donor nerve and/or its proximal stump. The direct connection is usually made to a healthy postlesional distal portion of a non-functioning nerve or implanted directly into denervated muscle or insensitive skin. Nerve sprouts will grow from the transferred nerve into the denervated elements and establish contact between them and the neurons that formerly controlled another area.
Transport proteins that carry specific substances in the blood or across cell membranes.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A transmembrane protein present in the MYELIN SHEATH of the CENTRAL NERVOUS SYSTEM. It is one of the main autoantigens implicated in the pathogenesis of MULTIPLE SCLEROSIS.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.
Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called CATHODE RAYS.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.
Proteins found in any species of bacterium.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
The techniques used to select and/or place only one embryo from FERTILIZATION IN VITRO into the uterine cavity to establish a singleton pregnancy.
Reduction in the number of lymphocytes.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Inflammation of the RETINA. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (CHORIORETINITIS) and of the OPTIC DISK (neuroretinitis).
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
Subset of helper-effector T-lymphocytes which synthesize and secrete IL-17, IL-17F, and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.
Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.
Glycoproteins found on the membrane or surface of cells.
Surgical removal of the thymus gland. (Dorland, 28th ed)
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The formation of one or more genetically identical organisms derived by vegetative reproduction from a single cell. The source nuclear material can be embryo-derived, fetus-derived, or taken from an adult somatic cell.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
Proteins prepared by recombinant DNA technology.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains.
Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.
Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.
The property of the T-CELL RECEPTOR which enables it to react with some antigens and not others. The specificity is derived from the structure of the receptor's variable region which has the ability to recognize certain antigens in conjunction with the MAJOR HISTOCOMPATIBILITY COMPLEX molecule.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Antibodies produced by a single clone of cells.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The number of LYMPHOCYTES per unit volume of BLOOD.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (sclera and cornea, and the retina). (Dorland, 27th ed)
The relationships of groups of organisms as reflected by their genetic makeup.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Allelic variants of the immunoglobulin light chains (IMMUNOGLOBULIN LIGHT CHAINS) or heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) encoded by ALLELES of IMMUNOGLOBULIN GENES.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms.
Infections with bacteria of the genus LISTERIA.
Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
A form of meningitis caused by LYMPHOCYTIC CHORIOMENINGITIS VIRUS. MICE and other rodents serve as the natural hosts, and infection in humans usually occurs through inhalation or ingestion of infectious particles. Clinical manifestations include an influenza-like syndrome followed by stiff neck, alterations of mentation, ATAXIA, and incontinence. Maternal infections may result in fetal malformations and injury, including neonatal HYDROCEPHALUS, aqueductal stenosis, CHORIORETINITIS, and MICROCEPHALY. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The ratio of the number of conceptions (CONCEPTION) including LIVE BIRTH; STILLBIRTH; and fetal losses, to the mean number of females of reproductive age in a population during a set time period.
Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.
A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
A classification of B-lymphocytes based on structurally or functionally different populations of cells.
The type species of ARENAVIRUS, part of the Old World Arenaviruses (ARENAVIRUSES, OLD WORLD), producing a silent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
A form of hypersensitivity affecting the respiratory tract. It includes ASTHMA and RHINITIS, ALLERGIC, SEASONAL.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
An individual that contains cell populations derived from different zygotes.
Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
A specialized subset of T-LYMPHOCYTES that exhibit features of INNATE IMMUNITY similar to that of NATURAL KILLER CELLS. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D ANTIGEN.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2.
Sites on an antigen that interact with specific antibodies.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
"Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice ... CTLA-4 plays a major role in suppressing the T-cell immune response. Without the proper functioning of CTLA-4 T-cells attack ... IL-2 promotes either immunity or tolerance in a concentration dependent fashion by acting on T helper cells, CTL and NK cells. ... May 2003). "Association of the T-cell regulatory gene CTLA-4 with susceptibility to autoimmune disease". Nature. 423 (6939): ...
"Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice ... In 2006, these claims were confirmed that even without spleen cells FCA can restore insulin producing beta cells in pancreas of ... This is related to the induction of Th17 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). Pancreatic ... Freund's complete adjuvant is effective in stimulating cell-mediated immunity and leads to potentiation of T helper cells that ...
and was also verified for HIV in the mouse model by adoptive transfer experiments. Non-human primate experiments also indicate ... This implies good quantity and quality of induced antibodies but low levels of T cell stimulation to avoid aforementioned ... The first step is based on a DNA vaccine vector in order to prime T cells. In the case of HIV, T cells specific for the group- ... Timewise the priming of T cells for Gag reduces the variation of the viral Env because of the lack of Env specific T cells ...
Provenge is an adoptive cell-transfer therapy in which a patient's antigen-presenting target autologous prostate cancer tissue ... control cell fate include strategies to induce pluripotent stem cell formation and using small molecules to induce stem cells ... In 2016 researchers transdifferentiated fibroblasts into induced neural stem cells. The team mixed the cells into an FDA- ... Another example is a T cell that targets only cells that display two separate markers. In 2016, John Lin head of Pfizer's San ...
The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant ... CISH is induced by T cell receptor (TCR) ligation and negatively regulates it by targeting the critical signaling intermediate ... The expression of this gene can be induced by IL-2, IL-3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated ... Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ...
... and adoptive cell transfer(ACT) therapy, was invented by RXi Pharmaceuticals and the Karolinska Institute. In this therapy, the ... February 2012). "mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients". ... June 2018). "Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of ... An mRNA molecule transfers a portion of the DNA code to other parts of the cell for making proteins. DNA therapeutics needs ...
More recently, CISH, another molecule with ubiquitin ligase activity, was found to be induced by T cell receptor ligation (TCR ... Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from ... CD4+ T cells can also promote tumor rejection. CD4+ T cells enhance CD8+ T cell function and can directly destroy tumor cells. ... The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant ...
"Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells". Biology of Blood and ... According to research some cancer-associated cells as well as tumor cells themselves can actively induce T cell exhaustion at ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... Gamma delta T cells[edit]. Gamma delta T cells (γδ T cells) represent a small subset of T cells that possess a distinct T cell ...
While most adoptive transfer experiments have been performed with tumor-specific CD8+ T cells, activated CD4+ T cell clones ... CD4+ T cells has already been successfully induced in non-small-cell lung carcinoma patients vaccinated with MAGE-3 recombinant ... This preference has been bolstered by numerous adoptive transfer studies in which CD8+ T cell lines and CD8+ clones specific ... T cell homing, T cell activation, and effector function. These effects are mediated at sites of T cell priming and at the tumor ...
Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, however for optimal ... Wilson, J.B.; J.L. Bell; A.J. Levine (1996). "Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in ... "Adoptive transfer of epstein-barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and ... This thereby inhibits the CD8-restricted cytotoxic T cell response against virus-infected cells. EBNA1 is expressed from the Qp ...
"Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells". Biology of Blood and ... According to research some cancer-associated cells as well as tumor cells themselves can actively induce T cell exhaustion at ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... Helper CD4+ T cellsEdit. T helper cells (TH cells) assist other lymphocytes, including maturation of B cells into plasma cells ...
... the adoptive transfer of cloned T cells in "in vitro immunization" caused increased frequencies of cancer fighting T cells in ... Chemically inducing this antigen in T-cells by DNA demethylation allows the immune system to recognize a wide range of tumors. ... Research on adoptive transfer in melanoma patients laid the groundwork for companies focusing on adoptive transfer research in ... CTLs and NK cells are both effector cells so helper T-cells (Th) are also prepared in order to create memory cells for long ...
HPV induced tumors). Adoptive cell transfer has been tested on lung and other cancers, with greatest success achieved in ... Adoptive cell transfer in vitro cultivates autologous, extracted T cells for later transfusion. Alternatively, Genetically ... Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell), cytotoxic T ... Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple ...
... and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor ... and/or Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space ... Suggested mechanisms include: Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts Induction ... Or-Geva N, Reisner Y (March 2016). "The evolution of T-cell depletion in haploidentical stem-cell transplantation". British ...
Killer-cell immunoglobulin-like receptor KLRC2 Adoptive cell transfer CD56 Human Cytomegalovirus IFN-γ Freud AG, Mundy-Bosse BL ... Similar to cytokine-induced memory-like NK cells, CD16 pre-activated NK cells up-regulate CD25 expression particularly in the ... Besides, it has been shown that the adoptive transfer of alloreactive NK cells does not cause graft-versus-host disease (GVHD ... CD56dim cNK cells can be a probable pool of progenitor cells for adaptive NK cells. The reason is that CD56dim cNK cells are ...
Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with ... Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med 2005;11(9):986-91. ... Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 2005;11(11 ... Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor ...
CD4+ T cells polarized with IL-23 and IL-6 are pathogenic upon adoptive transfer in type 1 diabetes while cells polarized with ... The protective and non-pathogenic Th17 cells induced by IL-6 and TGF-β are termed as Treg17 cells. The pathogenic Th17 cells ... Like other T helper cells, Th17 cells closely interact with B cells in response to pathogens. Th17 cells are involved in B cell ... In this way, Th17 cell lineage appears to be one of the three major subsets of effector T cells, as these cells are involved in ...
... and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor ... Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space niche. ... Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts ... subsequently actively transported into cancer cells. Once in the cells, the prodrug was enzymatically converted into the active ...
A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease" Blood 117 ... leading to leukemic cell proliferation and maturation or death; BCR-induced signals are likely delivered by common self ... Chiorazzi N, Ferrarini M. (2003) B Cell Chronic Lymphocytic Leukemia: Lessons learned from studies of the B cell antigen ... CS1 maint: discouraged parameter (link) "B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of ...
The TME can limit T cell viability. Both IDO and PD-L1 may induce T cell apoptosis. Myelomonocytic cell products that cause ... However, adoptive T cell therapy (ACT) with TILs has not had the dramatic success of ACT with virus-specific CD8+ T cells. The ... The discovery of melanoma-specific T cells in patients led to the strategy of adoptively transferring large numbers of in vitro ... Cancer cells induce apoptosis of activated T cells (a class of lymphocyte) by secreting exosomes containing death ligands such ...
The release of prolactin triggers the cells in the alveoli to make milk. Prolactin also transfers to the breast milk. Some ... It is also possible to induce lactation without pregnancy. Protocols for inducing lactation are called the Goldfarb protocols. ... and demonstrated with varying success in adoptive mothers. It appears plausible that the possibility of lactation in women (or ... When oxytocin binds to the myoepithelial cells, the cells contract. The increased intra-aveolar pressure forces milk into the ...
T-cell adoptive transfer[edit]. Adoptive cell transfer in vitro cultivates autologous, extracted T cells for later transfusion. ... CD56+ cells for inducing antihepatocellular carcinoma and antihepatitis C virus activity". J. Immunother. 34 (2): 129-38. doi: ... Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell), cytotoxic T ... Adoptive cell transfer has been tested on lung [13] and other cancers, with greatest success achieved in melanoma. ...
2005). "Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide ... 2005). "Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in ... "Multimer technologies for detection and adoptive transfer of antigen-specific T cells". Cancer Immunol Immunother. 2010 (59): ... which are used to detect antigen-specific T-cells in fluid cells and solid tissue samples using flow cytometry. These T-cells ...
... by T cells in melanoma patients and were likely the major contributor to positive clinical effects of adoptive cell transfer. ... Between 5.7 and 9.1% of individuals treated with ipilimumab develop checkpoint inhibitor induced colitis. Individual cases of ... It is undergoing[when?] clinical trials for the treatment of non-small cell lung carcinoma (NSCLC), small cell lung cancer ( ... The CTLs recognize the cancer cells by those antigens and destroy them. However, along with the antigens, the dendritic cells ...
ShK, ShK-Dap22, ShK-170 and PEGylated ShK-Q16K prevent adoptive-transfer EAE in Lewis rats, a model of multiple sclerosis. ... When naïve T cells and central memory T cells (TCM) are activated they upregulate KCa3.1 expression to ~500 per cell without ... Ovalbumin-induced delayed type hypersensitivity and oxazolone-induced dermatitis are considered to be models of atopic ... PEGylated ShK[Q16K] prevented adoptive-transfer experimental autoimmune encephalomyelitis in rats, a model for multiple ...
... has also been identified as candidate biomarker of adoptive T cell transfer therapy in metastatic melanoma. The role of ... "CXC Chemokine Ligand 9/Monokine Induced by IFN- Production by Tumor Cells Is Critical for T Cell-Mediated Suppression of ... Immune cells, like Th1, CTLs, NK cells, and NKT cells, show anti-tumor effect against cancer cells through paracrine CXCL9/ ... Programmed cell death-1 (PD-1) is heavily expressed on T cells at the tumor site than on T cells present in the peripheral ...
... and to improve adoptive cell transfer therapy. Sirolimus, which is the drug name for rapamycin, was approved by the U.S. Food ... Though AMPK induced eNOS has been shown to regulate mTORC1 in endothelium. Unlike the other cell type in endothelium eNOS ... Codogno P, Meijer AJ (Nov 2005). "Autophagy and signaling: their role in cell survival and cell death". Cell Death and ... In order for cells to grow and proliferate by manufacturing more proteins, the cells must ensure that they have the resources ...
Adoptive T cell therapy is a form of passive immunization by the transfusion of T-cells (adoptive cell transfer). They are ... The only approved cellular cancer therapy based on dendritic cells is sipuleucel-T. One method of inducing dendritic cells to ... Another approach is adoptive transfer of haploidentical γδ T cells or NK cells from a healthy donor. The major advantage of ... Cell types that can be used in this way are natural killer (NK) cells, lymphokine-activated killer cells, cytotoxic T cells and ...
Adoptive transfer of T cells expressing CARs is a promising anti-cancer therapeutic, because CAR-modified T cells can be ... which causes localized T cell activation. Anti-tumor activity in mice is induced only when both the universal CAR T cells plus ... "Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer". EMBO Molecular ... CAR-T cells can be either derived from T cells in a patient's own blood (autologous) or derived from the T cells of another ...
Passive or "adoptive transfer" of cell-mediated immunity, is conferred by the transfer of "sensitized" or activated T-cells ... Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies, which can be ... hematopoietic stem cells are transferred. When B cells and T cells are activated by a pathogen, memory B-cells and T- cells ... Passive immunity is acquired through the transfer of antibodies or activated T-cells derived from an immune host either ...
... Dimayuga ... Inhibitory effect on arterial injury-induced neointimal formation by adoptive B-cell transfer in Rag-1 knockout mice.}, volume ... indicating viable transfer of B cells. The results suggest that B cells modulate the response to arterial injury. (Less). Links ... indicating viable transfer of B cells. The results suggest that B cells modulate the response to arterial injury.}, author = { ...
FoxP3+ Treg cells. G-MSCs provide a promising approach for the treatment of autoimmune diseases. ... Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of Th1 ... The FoxP3+ Treg cells that were increased in frequency mainly consisted of Helios-negative cells. When Treg cells were depleted ... such as limited cell availability and reduced clinical feasibility. This study in mice with established collagen-induced ...
Development of a new cell therapy by adoptive transfer of regulatory T cells to induce immunological tolerance for the ... Although it has been reported that CD4^+ cells become regulatory T cells (Tr1 cells) when repeatedly stimulated with IL-10,IL ... Cell therapy. Research Abstract. (1)Generation of human regulatory CD4^+CD25^+ T cells. We confirmed that naive CD4^+ cells ... T cells generated ex vivo in skin transplantation model to examine whether transfer of those cells can prevent graft rejection. ...
... that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of ... specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) ... Here the authors show that transferred CD4+ gut intraepithelial lymphocytes can migrate into the CNS and inhibit inflammation ... Thus, the gut environment favours the generation of autoreactive CD4+ T cells with unique regulatory functions, potentially ...
Adoptive Transfer of T Cells.. Lymph node cells were depleted of macrophages, granulocytes, and CD8+ or CD4+ T cells by ... By contrast, in CD8+ T cell-containing mice, the bulk of transferred CD4+ T cells (CFSE+ CD4+ T cells) did not proliferate (Fig ... In nonlymphopenic animals, a cell subset other than CD8+ T cells (regulatory CD4 CD25+ T cells and CD4+ NK T cells in normal ... T cells transferred into CD3ɛ−/− Aβ−/− mice. CFSE-labeled CD4+ T cells from normal C57BL/6 mice were transferred into CD3ɛ−/− A ...
NK Cell Isolation and Adoptive Transfer.. NK cells were enriched from Rag1−/− splenocytes by negative selection using a mixture ... Previously-activated NK cells do not spontaneously produce cytokines 1-3 weeks after adoptive transfer. However, these NK cells ... NK cells were cultured for 5 h with cytokines before adoptive transfer (SI Materials and Methods). The next day cells were ... of cells producing IFN-γ before adoptive transfer. Several groups have recently shown that freshly isolated NK cells are poorly ...
Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular ... is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ... Here the authors show that elevation of intraocular pressure induces T cell infiltration in the eyes. Furthermore, they show ... Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma ...
Adoptive transfer. Spleen cells from WT or Jα18−/− mice were depleted of CD8+ T cells, CD62L+, and CD19+ B cells labeled with ... Adoptive transfer of iVα14 NKT cells, but not of spleen cells from Jα18−/− mice, fully restored the capacity of Jα18−/− mice to ... 3⇓E) in the serum of OVA-sensitized and -challenged Jα18−/− mice were restored by the adoptive transfer of iVα14 NKT cells. ... Adoptive transfer of WT iVα14 NKT cells fully reconstitutes the capacity of Jα18−/− mice to develop allergic asthma. Also, ...
... we performed adoptive transfer of labeled mature splenic NK cells into both m157-Tg and WT recipients. Transfer of WT NK cells ... Ly49H-mediated NK cell tolerance occurs quickly following adoptive transfer of mature NK cells. To better understand the time ... NK cells. Ly49H+ and Ly49H− NK cells from donor NK cells transferred into non-Tg mice produced similar levels of IFN-γ (Fig. 2B ... NK cells producing IFN-γ. The dot plots were gated on donor NK cells (NK1.1+, CD3−, CFSE+ cells). Donor cells were assessed 7 d ...
CD4+ and CD8+ T cell responses that were even higher in magnitude when compared to those induced by the virus, and this ... CD4+ and CD8+ T cell responses that were even higher in magnitude when compared to those induced by the virus, and this ... In this study we examined the efficacy of synthetic long peptides (SLPs) as a CD4+ and CD8+ T cell-eliciting preventive vaccine ... Our results show that the induction of strong T cell responses can be a fundamental component in the design of vaccines against ...
... mice after adoptive transfer of naive CD4+CD62LhiFoxp3.GFP− T cells. Sorted CD4+CD62LhiFoxp3.GFP− cells were adoptively ... PD-L1-induced CD4+Foxp3+ T reg cells suppress CD4+ T eff cells. To assess whether PD-L1-induced iT reg cells not only express ... WT T cells transferred into PD-L1−/−PD-L2−/− Rag−/− recipients could not convert to iT reg cells, suggesting that T cell-T cell ... PD-L1-induced CD4+ Foxp3+ T reg cells suppress CD4+ T eff cells in vitro. (A) PD-L1 iT reg cell function was assessed by [3H] ...
Chemotherapy and adoptive transfer. Rag1−/− mice were injected subcutaneously with 106 Melan-ret cells. When tumors became ... Transfection of RETAAD skin tumors with Cxcl9 induces T-cell infiltration. To directly show the role of CXCR3 ligands in T-cell ... Transcription of CCL5, CXCL9, and/or CXCL10 was induced in all tested cell lines, even though each cell line displayed a unique ... On day 6, tumors were analyzed for T-cell infiltration. A, the percentages of CD4+ and CD8+ T cells among total live cells in ...
Cell sorting and adoptive transfer.. Antigen-specific CD4+ BDC2.5 Teff and Treg cells were purified from transgenic mice on the ... Adoptive transfer of T cells to lymphopenic animals is followed by homeostatic proliferation and activation of the transferred ... For CD4+ BDC2.5 T cell analyses, the CD4+ Teff cells (n = 5 mice, 110 cells; mean ± SEM) and CD4+ BDC2.5 Treg cells (n = 5 mice ... We depicted the behavior of three major T cell lineages (CD4+ effector T [Teff] cells, CD4+ Treg cells, and CD8+ Teff cells), ...
Adoptive transfer experiments. For adoptive transfers, 0.5 × 106 OT-I Thy1.1 or 2 × 106 OT-II Ly5.1 T cells were negatively ... Vaccine-Induced Tumor Necrosis Factor-Producing T Cells Synergize with Cisplatin to Promote Tumor Cell Death. Tetje C. van der ... Enhanced cell death of TC-1 cells was accompanied by a TNFα-induced upregulation of the antiapoptotic molecule c-IAP2, and a ... The highest dose induced approximately 40% cell death and the lowest dose almost no cell death as measured by the MTT assays ( ...
We also found remarkably increased myeloid-derived suppressor cells (MDSCs) in tumor bearing mice, and depletion/transfer ... We also found remarkably increased myeloid-derived suppressor cells (MDSCs) in tumor bearing mice, and depletion/transfer ... Intracellular cytokine staining results showed that interferon-γ (IFN-γ) production in NKT cells, not CD4+ T cells, was ... Intracellular cytokine staining results showed that interferon-γ (IFN-γ) production in NKT cells, not CD4+ T cells, was ...
Adoptive transfer and re-isolation of T cells. Nfat1−/− or Nfat1+/+OT-II naïve CD4+ T cells or in vitro differentiated OT-II ... 105 B16 or B16-OVA cells and adoptively transferred with 5 × 106 OT-II CD4+ T cells. Transferred cells were re-isolated and ... Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are ... 105 B16-OVA cells followed by adoptive transfer of 5 × 106 naïve CD4+ T cells from C57Bl/6 or OT-II mice (A) or in vitro ...
... promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an ... Background: Adoptive transfer of immunosuppressive cells has emerged as a promising strategy for the treatment of immune- ... Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3- ... Keywords: Human monocyte-derived suppressor cells; T lymphocytes; graft-versus-host disease; inflammation; regulatory T cells; ...
Results indicated that CD4 cells are sensitized in vivo and migrate to the gastric mucosa where they induce gastritis in ... Adoptive Transfer of Splenocytes in SCID Mice Implicates CD4+ T Cells in Apoptosis and Epithelial Proliferation Associated with ... Recipient mice differed, however, according to the source of the transferred CD4+ cells. The CD4+ cell scores for recipients of ... cell scores did not become significantly high until two weeks after transfer (postinoculation week 6) in recipients of cells ...
When polarized to a Th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. Histology ... Animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that ... In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies ... The potential role of T cells in the central nervous system, however, has not been thoroughly examined. We generated an anti- ...
... adoptive transfer of the antiergotypic T cells induced significant protection from AA; control rats that had received LN cells ... adoptive transfer of antiergotypic T cells protected rats from AA; (d) antiergotypic T cells responding to whole T cells could ... T cells compared with 5-6% TCRγ/δ+ cells in the CD8+ T cells that had been purified from whole DLN cells. The purified cells ... Adoptive transfer of antiergotypic T cells protects from AA. Antiergotypic T cells were obtained from the DLN of rats ...
NKT cells remain anergic upon adoptive transfer. Mice were injected with α-GalCer or vehicle and sacrificed on day 3. NKT cells ... α-GalCer-induced NKT cell anergy is cell autonomous. Recent studies have suggested a role of regulatory T cells and tolerogenic ... Peripheral NKT cell unresponsiveness induced by α-GalCer resembled the tolerance that is induced in conventional T cells by ... NKT cell anergy is cell autonomous and does not exhibit dominant suppression. (A) NKT cell anergy is predominantly cell ...
T cell purification, CFSE labelling, adoptive transfer and antigen‐induced arthritis. Untouched CD4+ T or CD8+ T cells were ... PD‐L1 co‐stimulation contributes to ligand‐induced T cell receptor down‐modulation on CD8+ T cells. Katarzyna Karwacz, ... We show here that binding of PD‐L1 on dendritic cells to PD‐1 on T cells is implicated in ligand‐induced TCR down‐modulation, ... between 106 and 108 cells/mouse) into groups of five mice, when indicated. After transfer, antigen‐induced arthritis was ...
Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial ... Adoptive Transfer Adult Aged CD8-Positive T-Lymphocytes - drug effects - immunology - pathology Cell Aging Cell Proliferation ... Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats. ... For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by ...
Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis. ... PD-1 genotype of the donor is associated with acute graft-versus-host disease after HLA-identical sibling donor stem cell ... Different roles of Nrf2 and NFKB in the antioxidant imbalance produced by esculetin or quercetin on NB4 leukemia cells. ... Myocardial fibrosis as a matter of cell differentiation: opportunities for new antifibrotic strategies. ...
Adoptive transfer.Passive/adoptive transfer was performed as described previously (18). Briefly, serum (200 μl) or ... Adoptive transfer of anti-SPY1 antibody conferred protection to naive μMT mice, and immune T cells were indispensable to ... Bacteria were added to HL-60 cells at a ratio of 10:1 (bacteria to cells; 4 × 105 cells). Killing was defined as the percent ... Many studies have shown that the protection induced by living vaccine depends not only on the effect of B cells but also on the ...
Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. ... Splenic dendritic cells from the non-obese diabetic mouse induce a prolonged proliferation of syngeneic T cells. A role for an ... linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell ... Notch activation in thymic epithelial cells induces development of thymic microenvironments.. Masuda K, Germeraad WT, Satoh R, ...
Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal ... T cells, 7.9% B cells) or B cells (84.2% B cells, 8.3% T cells), and transferred into naïve mice i.n. At 3 hours posttransfer, ... transfer of enriched T cells (A) or B cells (B) or received no transfer (C). Three hours after cell transfer, mice were ... Adoptive transfer of γ-A/PC-immune T cells, but not B cells, provides protection from heterosubtypic challenge. Immune splenic ...
Adoptive transfer of T cells.The adoptive transfer protocol was modified from a method described previously (9, 33). The ... T cells induced by NP DNA is not known. Studies using adoptive transfer of T cells from influenza virus-infected mice into ... Adoptive transfer of T-cell subsets. Spleen cells from uninjected mice (solid triangles) or mice primed with influenza virus A/ ... Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as ...
... induced regulatory cells that could inhibit the adoptive transfer of diabetes by pathogenic effector T cells. In the classic ... Adoptive transfer of diabetes is suppressed by CD8 γδ T cells induced by aerosol insulin: summary of 11 experiments. ... Adoptive transfer of diabetes is suppressed by CD8 γδ T cells induced by aerosol insulin: summary of 11 experiments. ... Aerosol insulin induces CD8 T cells that suppress the transfer of diabetes. 6-9-wk-old NOD male mice (n = 16 per group) were ...
Inhibition of PNT production improves the antitumor effect of adoptive T cell transfer. ... Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice.. Lu T1, Ramakrishnan R, Altiok S, ... Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice ... Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice ...
  • Therefore, identifying chemotherapeutic drugs able to induce the expression of T-cell-attracting chemokines in cancer cells may represent a novel strategy to improve the efficacy of cancer immunotherapy. (
  • T-cell recruitment to the tumor is one of the potential rate-limiting steps in immunotherapy, and thus, intratumoral chemokines are likely to have a major impact ( 11, 12 ). (
  • By illustrating the dependence of tumor-induced CD4+ T-cell anergy on NFAT1, our findings open the possibility of targeting this transcription factor to improve the efficacy of cancer immunotherapy or immunochemotherapy. (
  • Target autoantigens that trigger or drive immune reactivity to β cells not only have diagnostic applications, but are potential agents for specific immunotherapy ( 5 - 8 ). (
  • The use of allogeneic, pluripotent stem cell-derived immune cells for cancer immunotherapy has been the subject of recent research, including clinical trials. (
  • Hu Y, Tian ZG, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. (
  • Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for cancer immunotherapy. (
  • Car-based strategies beyond t lymphocytes: integrative opportunities for cancer adoptive immunotherapy. (
  • 1999) Immunotherapy of human tumors with T-cell-activating bispecific antibodies: stimulation of cytotoxic pathways in vivo. (
  • 2000) In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem cell transplantation in children with solid tumors. (
  • The most appealing element to this approach, termed antigen-specific immunotherapy (ASI), has been that it not only provides an effective means of controlling the autoimmune response via induction or restoration of β-cell-specific tolerance, but that it may achieve these goals without major concerns over safety and certainly without the specter of immune suppression. (
  • Immunotherapy with adoptive T-cell transfer (ACT) achieves responses in patients with melanoma, but most patients develop resistance and eventually relapse. (
  • An emerging strategy for cancer immunotherapy involves genetic manipulations that program tumor-killing capabilities into patient or donor T cells. (
  • Our results provide new insights into quantitative and qualitative requirements of vaccine-elicited functional CD8(+) T cells in cancer prevention and immunotherapy. (
  • The HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore potential targets for T cell mediated adoptive immunotherapy. (
  • Effective immunotherapy is dependent on the presence of both CD4+ and CD8+ T cells. (
  • A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. (
  • Tumor immunotherapy with T lymphocytes, which can recognize and destroy malignant cells, has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens. (
  • Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. (
  • Continued clinical efficacy demonstrations of cell-based immunotherapies (iTx) such as chimeric antigen receptor T cell (CAR-T) therapies has made the prospect increasingly likely of an immunotherapy product achieving conditional market authorization in the short term. (
  • Consequently, a team of scientists led by the lab Melody Swartz at EPFL (now at the University of Chicago) with co-first authors Manuel Fankhauser and Maria Broggi hypothesized that VEGF-C induced lymphangiogenesis and immune suppression would hinder the effectiveness of immunotherapy. (
  • Once in the tumor, these naïve T cells are locally activated following immunotherapy-induced tumor cell death, which triggers a positive feedback loop of long-lasting anti-tumor immunity. (
  • The team tested their hypothesis on different mouse models of melanoma using multiple immunotherapy approaches, including vaccination and adoptive T cell transfer. (
  • But when the scales are tipped toward activating factors dominating over suppressive ones, as is the case with immunotherapy, these T cells become robust participants in antitumor immunity. (
  • In this issue of Blood , Sugata et al report that vaccination against human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper (bZIP) factor (HBZ) could be used for immunotherapy in adult T-cell leukemia-lymphoma (ATL) patients. (
  • Inhibitory effect on arterial injury-induced neointimal formation by adoptive B-cell transfer in Rag-1 knockout mice. (
  • We investigated the effect of B-cell reconstitution in immune-deficient Rag-1 knockout (KO) mice subjected to arterial injury. (
  • To investigate the role of B cells in response to injury, Rag-1 KO mice were reconstituted with B cells derived from the spleens of WT mice, with donors and recipients on the same diet. (
  • Reconstitution of Rag-1 KO mice with B cells from WT mice. (
  • Injured carotid arteries from reconstituted Rag-1 KO mice had detectable IgM and IgG, indicating viable transfer of B cells. (
  • This study in mice with established collagen-induced arthritis (CIA) was undertaken to determine whether substitution of human gingiva-derived mesenchymal stem cells (G-MSCs) would significantly improve the therapeutic effects. (
  • CIA was induced in DBA/1J mice by immunization with type II collagen and Freund's complete adjuvant. (
  • In some experiments, intraperitoneal injection of PC61 (anti-CD25 antibody) was used to deplete Treg cells in arthritic mice. (
  • Infusion of G-MSCs also resulted in increased levels of CD4+CD39+FoxP3+ cells in arthritic mice. (
  • Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. (
  • Recolonizing GF mice with a full complement of commensal bacteria or even with segmented filamentous bacteria alone restored gut T H 17 cells in mice, along with the ability of the mice to develop EAE 3 . (
  • Myelin oligodendrocyte glycoprotein (MOG)-specific T-cell receptor (TCR) transgenic (2D2) mice 15 are often used to study MS pathogenesis, as a proportion of these mice spontaneously develop EAE several months after birth. (
  • Although precise mechanisms are not fully understood, pathogenesis in 2D2 mice may depend on the balance between monoclonal T cells with pathogenic potential and those with regulatory functions. (
  • Here we show that expansion, but not short-term survival, of CD4 + T cells depends on interactions with MHC class II molecules in lymphopenic mice. (
  • Nevertheless, interactions with classical MHC class II molecules are required for CD4 + T cells to survive in CD8 + T-cell-containing mice. (
  • Mice deficient for the expression of MHC class I and/or MHC class II molecules have been used to address the role of self-peptide/self-MHC molecule complexes in the viability of peripheral T cells. (
  • Most of the studies of CD4 + T cell survival have been performed by using I-A β -deficient H-2 b mice (A β −/− mice) as MHC class II-deficient hosts ( 4 - 10 ). (
  • First, on the basis of the disappearance of CD4 + T cells in these mice, survival of peripheral CD4 + T cells was proposed to depend on permanent interactions with MHC class II molecules expressed on peripheral antigen-presenting cells (APCs) ( 4 , 5 , 7 ). (
  • Nevertheless, two different groups have recently observed that CD4 + T cells disappeared with similar kinetics in both normal and A β −/− mice ( 8 , 9 ). (
  • The fact that naive T cells do not cycle in the periphery of normal adult mice in the absence of antigenic stimulation has been considered to result from the process of negative selection in the thymus. (
  • However, it has been shown recently that naive T cells proliferate in response to self-peptide/self-MHC molecule complexes in neonatal mice ( 11 ) and after transfer into lymphopenic hosts ( 12 - 22 ). (
  • For this reason, we have studied the fate of CD4 + T cells transferred into mice lacking the expression of classical MHC class II molecules (A β −/− mice) as a function of the ability of recipient mice to produce endogenous T cells. (
  • In this article, we show that although CD4 + T cells transferred into A β −/− mice disappear, most of these cells survive and slowly cycle after transfer into CD3ɛ −/− A β −/− mice. (
  • Such an expansion was not observed after transfer into lymphopenic MHC II Δ/Δ mice, these mice lacking the expression of both α and β chains of I-A and I-E MHC class II molecules ( 24 ), implying that in A β −/− mice, A α chain and E β chain associate to form a hybrid A α E β MHC class II molecule. (
  • Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. (
  • Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. (
  • mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. (
  • As HSPs are among the most highly conserved proteins from bacteria to mice to humans (up to 60% identity) 10 , a possibility is that the anti-HSP immune responses are induced originally by bacterial HSPs, and are reactivated by host HSPs during glaucoma. (
  • and (4) HSP-specific CD4 + T-cell responses and glaucomatous neurodegeneration are both abolished in mice raised in the absence of commensal microbial flora (germ-free (GF) mice), supporting a mechanism of bacteria sensitized T-cell responses underlying the pathogenesis of glaucoma. (
  • In this paper, we show that OVA-immunized Jα18 −/− mice, which are exclusively deficient in the invariant Vα14 + (iVα14), CD1d-restricted NKT cells, exhibit impaired AHR and airway eosinophilia, decreased IL-4 and IL-5 production in bronchoalveolar lavage fluid, and reduced OVA-specific IgE compared with wild-type (WT) littermates. (
  • Adoptive transfer of WT iVα14 NKT cells fully reconstitutes the capacity of Jα18 −/− mice to develop allergic asthma. (
  • Also, specific tetramer staining shows that OVA-immunized WT mice have activated (CD69 + ) iVα14 NKT cells. (
  • Adoptive transfer of effector Th2 cells into naive mice followed by exposure to inhaled Ags triggers eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness, definitively demonstrating the capacity of immune Th2 cells to induce the asthma phenotype ( 3 ). (
  • Furthermore, mature Ly49H-expressing NK cells from wild-type mice can acquire a tolerant phenotype by 24 h posttransfer into a transgenic C57BL/6 mouse that expresses m157. (
  • The tolerant phenotype can be reversed, in vivo, if tolerant NK cells are transferred to mice that do not express the m157 protein. (
  • The Ly49H activation receptor, which is expressed on a subset of NK cells in C57BL/6 mice, is coupled to the DAP12 adaptor protein. (
  • Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression of these chemokines and favored T-cell infiltration into cutaneous tumors. (
  • Previously, we have shown that synthetic long peptides (SLP) vaccination against human papillomavirus type 16 (HPV16) oncogenic proteins is safe and induces functional T-cell responses in mice and humans. (
  • Although vaccination induces potent clinical responses in mice and in patients with premalignant lesions, no clinical responses were observed in patients with cervical cancer. (
  • In this report, we studied the liver immune response of tumor-bearing (TB) mice using concanavalin A (Con A)-induced hepatitis model. (
  • We also elucidated that large amounts of myeloid-derived suppressor cells (MDSCs) being influx into the liver in TB mice and these MDSCs were essential for liver immune suppression through both depletion and reconstitution approaches. (
  • MDSCs, a heterogeneous of immune cells including immature DCs, macrophages, granulocytes, and other myeloid cells in early stages of their differentiation, usually express CD11b, CD33, and low levels of leukocyte antigen-DR in humans or CD11b and Gr1 in mice ( 7 , 8 ). (
  • Furthermore, by specifically targeting the regulation of anergy induction using NFAT1-deficient mice, our results support that tumor-induced CD4+ T-cell anergy participates in the evasion of antitumor responses, as NFAT1-deficient T cells become resistant to tumor-induced anergy, delaying tumor appearance and slowing tumor growth. (
  • Of therapeutic relevance, HuMoSCs induce long-lasting memory forkhead box protein 3-positive CD8+ regulatory T lymphocytes and significantly reduce GvHD induced with human PBMCs in NSG mice. (
  • We generated an anti-AQP4 antibody seronegative model of NMO using pathogenic AQP4-reactive T cells in mice by immunizing AQP4 null mice with peptides corresponding to the second extracellular loop of AQP4, loop C. When polarized to a Th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. (
  • In summary, we show that AQP4-reactive T cells are sufficient to trigger an NMO-like disease in mice, independent of antibodies, indicating that pathogenic AQP4-reactive T cells may play a similar role in humans. (
  • We used a unique approach to raise pathogenic AQP4-reactive T cells by immunizing AQP4 null mice with loop C peptide of AQP4 (AQP4 135-153 ). (
  • When adoptively transferred into wild type mice after re-stimulation in culture with Aqp4 135-153 peptide, behavioral disease was not induced though mild T cell infiltration of the central nervous system (CNS) was observed. (
  • Here, we show that a single administration of the synthetic glycolipid α-galactosylceramide (α-GalCer) induces long-term NKT cell unresponsiveness in mice. (
  • Consequently, we found that activation of anergic NKT cells with α-GalCer exacerbated, rather than prevented, B16 metastasis formation, but that these cells retained their capacity to protect mice against experimental autoimmune encephalomyelitis. (
  • The H. pylori -infected and uninfected C57BL/6J and recipient SCID mice were evaluated to detect CD4 + and CD8 + T cells, B cells, apoptotic epithelial cells, and epithelial cell proliferation at postinoculation weeks 5, 6, 8, and 12. (
  • In all H. pylori -infected mice, gastric CD4 + cell scores were increased, compared with scores for uninfected controls. (
  • Recipient mice differed, however, according to the source of the transferred CD4 + cells. (
  • The CD4 + cell scores for recipients of splenocytes from H. pylori -infected (immune) donors were indistinguishable from those for wild-type donor mice at all time points. (
  • Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. (
  • Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. (
  • The mechanism for this cross-protection has been studied extensively in mice immunized with live, replicating influenza virus and has been attributed to cross-reactive cytotoxic T (Tc) cells ( 11 , 26 , 37 , 44 , 45 , 56 , 57 ). (
  • In addition, heterosubtypic immunity has been reported for β 2 -microglobulin-deficient (Tc-cell-response-deficient) ( 14 , 38 , 55 ) and gamma interferon (IFN-γ)-deficient mice ( 39 , 44 ). (
  • Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al. (
  • In the present study, we have analyzed in detail the cellular immune responses induced by influenza virus nucleoprotein (NP) DNA and have established that both CD4 + T cells secreting Th1-type cytokines and CD8 + cytotoxic T cells play important effector roles in heterosubtypic protective immunity against lethal influenza virus challenge in mice. (
  • The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 γδ T cells. (
  • Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. (
  • In a previous study, we found that in mice, myeloid-derived suppressor cells (MDSCs) are a source of the free radical peroxynitrite (PNT). (
  • We investigated the effects of IL-10 administered in combination with rapamycin on the induction of Tr1 cells that could mediate a state of tolerance in diabetic mice after pancreatic islet transplantation. (
  • Tr1 cells that produced high levels of IL-10 and suppressed T-cell proliferation were isolated from splenocytes of rapamycin plus IL-10-treated mice after treatment withdrawal. (
  • CD4 + T-cells from rapamycin plus IL-10-treated mice transferred antigen-specific tolerance in mice that received new transplants. (
  • Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. (
  • Chronic pressure overload (6 weeks transaortic constriction, TAC) induced a decrease in cardiac function in WT mice but not in animals expressing truncated βIV-spectrin lacking spectrin/CaMKII interaction (qv3J). (
  • Using CD37-deficient mice, the group demonstrated that loss of CD37 expression results in spontaneous, multiple-organ lymphoma that consists of IgA + , germinal center-like B cells. (
  • Adoptive transfer of CD37-deficient lymphoma cells to CD37-deficient or lymphocyte-deficient recipient mice induced new tumors with metastatic potential. (
  • Mice lacking CD37 developed germinal center-derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice. (
  • Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. (
  • Experimental autoimmune uveitis (EAU) induced in mice using the retinal antigen interphotoreceptor retinoid binding protein (IRBP) is an animal model for posterior uveitis in humans. (
  • This made it possible to design MHC tetramers and use them to detect epitope-specific T cells in the uveitic eye and in lymphoid organs of hIRBP651-670-immunized mice. (
  • 1 , 2 Experimental autoimmune uveitis (EAU) induced in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) is an animal model used to represent these diseases and has been extremely useful to define basic mechanisms of disease as well as a template to evaluate new therapies. (
  • Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55 −/− but not p75 −/− mice. (
  • The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55 −/− mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. (
  • After onset of arthritis, mice were treated with soluble TNFR-Fc for 10 d and the production of IL-17 and IFNγ by LN cells was determined by ELISA. (
  • Significantly increased IL-17 and IFNγ production was observed after stimulation of LN cells from TNFR-Fc-treated mice with collagen or anti-CD3 mAb in vitro, and a trend toward enhanced production of these cytokines was observed even in unstimulated LN cells ( Fig. 1 ). (
  • Recently, a substantial number of these innate CD8 + T cells was also identified in wild-type BALB/c mice [ 6 ] and in human [ 14 ]. (
  • Promyelocytic leukemia zinc finger protein (PLZF) + NKT cells are the major source of IL-4 in wild-type BALB/c and Klf2-deficient mice [ 6 ], whereas in CIITA Tg mice PLZF + T-T CD4 + T cells are responsible for the production of IL-4 [ 14 , 15 ]. (
  • Secondly, MHC class Ib-restricted innate T cells have a highly restricted TCR repertoire [ 16 ], whereas IL-4-induced Eomes + innate CD8 + T cells from CIITA Tg mice have a diverse TCR repertoire very much like conventional T cells [ 14 ]. (
  • Recently an alternative resistance mechanism has been observed in mice: inflammation-induced dedifferentiation of tumor cells to precursor cells of neural crest origin results in loss of the tumor antigen. (
  • First, they transgenically transferred the genetic information for a repertoire of human TCRs into mice, thus developing an arsenal of T cells expressing human receptors. (
  • When human cancer antigens are subsequently inoculated into these mice, they are of course perceived as foreign and induce reactive T cells. (
  • Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. (
  • Transgenic mice generate human T cell receptors that recognize cancer cells as foreign. (
  • Here we examined the effects of adaptive and innate immune cells-cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells-that share the direct perforin-mediated cytotoxic pathway on outcome after cerebral ischemia in mice. (
  • Correspondingly, adoptive CTL transfer from wild-type into Rag1 knock-out mice increased infarct size. (
  • Adoptive CTL transfer from perforin knock-out or interferon-γ knock-out mice into Rag1 knock-out mice revealed that CTL neurotoxicity was mediated by perforin. (
  • Accordingly, CTLs isolated from wild-type or interferon-γ knock-out but not from perforin knock-out mice induced neuronal cell death in vitro. (
  • CTLs derived from ovalbumin-specific T-cell receptor transgenic mice were not activated and infiltrated less into the ischemic brain compared with wild-type CTLs. (
  • Their transfer did not increase the infarct size of Rag1 knock-out mice, indicating antigen-dependent activation as an essential component of CTL neurotoxicity. (
  • The role of contact-dependent signaling in the development of experimental allergic encephalomyelitis has been shown dramatically using transgenic B10.PL mice expressing the T cell receptor reactive with the encephalitogenic peptide (Ac1-11) of myelin basic protein. (
  • The adoptive transfer of CD80-positive accessory cells into CD40L-deficient mice restored their ability to respond to antigen and to develop experimental allergic encephalomyelitis. (
  • In this study, the function of primary T cells expressing such receptors has been investigated in transgenic mice. (
  • Adoptive transfer of autoreactive CD4 + T cells (OT-II mice) led to autoantibody (anti-lysozyme) production by B cells in multiple anatomic compartments, including the bone marrow. (
  • Conclusions These data demonstrate that B cells autoreactive to RBC antigens survive in healthy mice with normal immune systems. (
  • Fig. 1 Population alterations of MCs, ILC2s, and IL-10 + B reg cells in CHS mice. (
  • C ) Data for the ear thickness and ( D ) the number of IL-13 + ILC2s in Cd19 Cre mice with CHS are shown after the adoptive transfer of OXZ-sensitized WT or Il10 −/− B cell subsets as indicated. (
  • More importantly, administration of the recombinant FGF2 protein significantly alleviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice. (
  • Based on the results from experiments in which neutrophils were depleted and adoptively transferred, FGF2 protected mice against IAV infection by recruiting neutrophils. (
  • 2015) showed that FGF2 is required for epithelial repair and maintaining epithelial integrity after bleomycin-induced lung injury in mice. (
  • Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. (
  • Moreover, the adoptive transfer of naturally occurring Tregs CD4 + CD25 + CCR5 + , CD4 + CD25 − CCR5 + or CD8 + CCR5 + conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. (
  • Interestingly, adoptive transfer of WT CD4 + CD25 + CCR5 + cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. (
  • Adoptive transfer of T cells isolated from tumor-bearing mice treated with the vaccine inhibited growth of tumors in unvaccinated recipients. (
  • Methods Unilateral cerebral ischaemia was induced in mice by occlusion of one middle cerebral artery (MCAO) at different time points after induction of G6PI-induced arthritis in mice. (
  • Regulatory T cells were specifically depleted by injection of diphtheria toxin into transgenic DEREG mice. (
  • The role of NOD2, MyD88 and interleukin 10 (IL-10) in this protection was studied using Nod2 −/− , MyD88 −/− and Il10 -deficient mice, while induction of regulatory dendritic cells (DCs) was monitored through the expansion of CD103 + DCs in mesenteric lymph nodes or after adoptive transfer of bone marrow-derived DCs. (
  • PGN purified from Ls33 rescued mice from colitis in an IL-10-dependent manner and favoured the development of CD103 + DCs and CD4 + Foxp3 + regulatory T cells. (
  • In 2006, these claims were confirmed that even without spleen cells FCA can restore insulin producing beta cells in pancreas of NOD mice. (
  • Recombinant activating gene-1 ( Rag-1 ) -/- mice, lacking both T and B cells, were used. (
  • Male and female Rag-1 -/- mice received adoptive transfer of male CD3 + T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). (
  • These results suggest that female Rag-1 -/- mice are protected from male T-cell-mediated increases in Ang II-induced hypertension when compared with their male counterparts, and this protection may involve sex differences in the magnitude of T-cell infiltration of the kidney and brain. (
  • T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. (
  • Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17‐(dimethylaminoethylamino)‐17‐demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. (
  • DMAG treatment was, however, insufficient to prolong overall survival of leukemia‐bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. (
  • However, the observation that T cells from CD40L-deficient mice are capable of contact-dependent signaling of macrophages (31) establishes that membrane-anchored receptor:ligand pairs other than CD40:CD40L can be involved in T cell signaling of macrophages. (
  • referred to as aPIK3CD) and intercrossed these mice with B cell-specific Cre models. (
  • Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. (
  • Finally, Mb1-aPIK3CD mice exhibited blunted T cell-independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell-dependent immunization. (
  • Naïve mice were inoculated intraperitoneally with lymphoma cells expressing HTLV-1 HBZ and then with peptide-stimulated splenocytes from rVV-HBZ-vaccinated mice. (
  • The study by Sugata et al 1 aimed to determine whether a recombinant vaccinia virus expressing HBZ as an antigen (rVV-HBZ) would elicit specific T-cell responses and whether this vaccine could be used to treat mice inoculated with HBZ lymphoma cells. (
  • More interestingly, CD4 + T cells isolated from HBZ-transgenic animals were efficiently eliminated when transferred to HBZ-vaccinated mice. (
  • More importantly, Sugata et al 1 showed that adoptive transfer of splenocytes obtained from rVV-HBZ-vaccinated mice significantly improved the survival of animals inoculated with transformed T cells that express only HBZ, as do most ATL cells (see figure). (
  • Caption: Figure 2: Alloantigen immune tolerance is transferable by adoptive transfer of CD4+ T cells from long-lasting tolerant mice. (
  • Adoptive transfer of splenic lymphocytes from immunized animals protected suckling mice against murine rotavirus-induced gastroenteritis in the absence of rotavirus-specific neutralizing antibodies, indicating that antigen-specific CTLs protect against mucosal pathogens in the intestinal tract (32). (
  • In addition, survival of skin allografts was prolonged after adoptive transfer of MDSC from ILT2 transgenic mice and histologic evaluation of the allografts, showing that MDSCs from ILT-2 transgenic mice were recruited to the graft. (
  • Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing th17 responses in mice and patients. (
  • Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. (
  • Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. (
  • Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. (
  • CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. (
  • ACT of splenocytes from fully immunocompetent mice transduced with a chimeric murine/human TCR specific for tyrosinase, together with lymphodepletion conditioning, dendritic cell (DC)-based vaccination, and high-dose interleukin-2 (IL-2), had profound antitumor activity against large established MHC- and antigen-matched tumors. (
  • ACT of splenocytes from fully immunocompetent HLA-A2.1/K(b) mice transduced with a chimeric murine/human TCR specific for tyrosinase, together with lymphodepletion conditioning, dendritic cell (DC)-based vaccination, and high-dose interleukin-2 (IL-2), had profound antitumor activity against large established MHC- and antigen-matched tumors. (
  • In target tissue, Foxp3 + regulatory T (T reg ) cells persistently contacted T eff cells with or without involvement of CD11c + dendritic cells, an observation conciliating with the in vitro "trademark" of T reg function, contact-dependent suppression. (
  • Dendritic cells (DC) in tumor microenvironments seem to play a crucial role in the induction of anergy in CD4+ T cells ( 9 ). (
  • Here, we show that the interaction between programmed cell death 1 ligand 1 (PD‐L1) on dendritic cells (DCs) and programmed death 1 (PD‐1) on CD8 T cells contributes to ligand‐induced TCR down‐modulation. (
  • This process limits TCR signal transduction and prevents T cell hyperactivation after antigen‐presentation by dendritic cells. (
  • We show here that binding of PD‐L1 on dendritic cells to PD‐1 on T cells is implicated in ligand‐induced TCR down‐modulation, by promoting Cbl‐b E3 ubiquitin ligase expression. (
  • By combining PD‐L1 silencing with modulators of selected signalling pathways (MAPKs) in dendritic cells, we have increased their anti‐tumour activities, obtaining therapeutic effects with doses 100‐to‐1000‐fold lower than those currently used in experimental cancer models and in human clinical trials. (
  • Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be rescued for full effector function. (
  • Interruption of dendritic cell-mediated TIM-4 signaling induces regulatory T cells and promotes skin allograft survival. (
  • Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. (
  • β-cell damage is a result of the combined actions of proinflammatory helper T cells (T H 1) and cytotoxic T lymphocytes (CTL), which are primed against islet autoantigens such as GAD65 (GAD) and preproinsulin (INS) by inflammatory dendritic cells (DCs). (
  • Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). (
  • This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cells in vivo . (
  • This nonresponsiveness was ascribed to the inability of CD40L-deficient T cells to induce CD80 expression on dendritic cells. (
  • T helper cells and to a lower degree monocytes and dendritic cells express CD4. (
  • Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. (
  • Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. (
  • Both lesions contain monocyte/macrophages and T cells (3) and putative dendritic cells (4), and both lesions have a broadly Th1 cytokine profile (5). (
  • We are planning to use those CD4^+CD25^+ T cells generated ex vivo in skin transplantation model to examine whether transfer of those cells can prevent graft rejection. (
  • Using a transgenic mouse model, we demonstrate that induction of tolerance in Ly49H + NK cells by chronic exposure to m157, in vivo, requires signaling through the Ly49H adaptor protein DAP12, but not the DAP10 adaptor protein. (
  • Thus, continuous activating receptor engagement can induce a transient tolerance in mature NK cells in vivo. (
  • The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1 −/− PD-L2 −/− Rag −/− recipients of naive CD4 T cells. (
  • . In vivo neutralization of TNFα significantly reduced the antitumor responses induced by the combined treatment. (
  • Here, using a B16 melanoma tumor model expressing the tumor surrogate antigen chicken albumin (OVA), we show that tumor antigen specific CD4+ T cells are rendered anergic in vivo through a mechanism that requires NFAT1 activity and involves the expression of anergy specific genes. (
  • However, only a limited number of such cells can be isolated from in vivo specimens. (
  • Therefore efficient ex vivo differentiation and expansion procedures are critically needed to produce a clinically relevant amount of these suppressive cells. (
  • We sought to develop a novel, clinically relevant, and feasible approach to generate ex vivo a subpopulation of human suppressor cells of monocytic origin, referred to as human monocyte-derived suppressive cells (HuMoSCs), which can be used as an efficient therapeutic tool to treat inflammatory disorders. (
  • Ex vivo-generated HuMoSCs inhibit effector T lymphocytes, promote the expansion of immunosuppressive forkhead box protein 3-positive CD8+ regulatory T cells, and can be used as an efficient therapeutic tool to prevent GvHD. (
  • The in vivo dynamics of the NKT cell population in response to glycolipid activation remain poorly understood. (
  • Interference with PD‐L1/PD‐1 signalling markedly inhibits TCR down‐modulation leading to hyper‐activated, proliferative CD8 T cells as assessed in vitro and in vivo in an arthritis model. (
  • Results indicated that CD4 cells are sensitized in vivo and migrate to the gastric mucosa where they induce gastritis in response to H. pylori antigens. (
  • It has been reported that in vivo depletion of CD4 + or CD8 + T cells ( 8 , 14 , 28 , 30 , 41 ) or of both T-cell subsets ( 14 ) had only a minor effect on heterosubtypic protection. (
  • Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA. (
  • Thus rapamycin plus IL-10 not only prevented allograft rejection but also induced Tr1 cells that mediated stable antigen-specific, long-term tolerance in vivo. (
  • After being activated with their specific antigen, Tr1 cells regulate the responses of naïve and memory T-cells in vitro and in vivo and can suppress Th1 cell-and Th2 cell-mediated pathologies ( 4 ). (
  • We also observed toll-like receptor 7 agonist-induced reductions in SIV DNA and ex vivo inducible virus from treated animals. (
  • Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. (
  • The second-generation CIR (termed "Tandem" for two signals) was designed to transmit TCR Signal 1 and CD28 Signal 2 to render T cells resistant to AICD and provide prolonged antitumor effect in vivo . (
  • An advanced generation of anti-CEA designer T cells is described with features that promise a more potent and enduring antitumor immune response in vivo . (
  • The use of tumor-infiltrating lymphocytes (TIL) in patients with melanoma or renal cell carcinoma possessed a rationale based on a native but weak response of the host to the tumor before therapeutic intervention that was augmented by ex vivo manipulation and re-administration with interleukin-2 (IL-2) supplementation ( 1 ). (
  • This strategy has the advantage that peripheral blood cells may be used without resort to tumor sampling and the associated challenges of tumor-induced propagation of T cells ex vivo . (
  • On this basis, it would be predicted that TNFα blockade would result in reduced IL-17 expression, and to test this hypothesis in vivo, we investigated the dependence of IL-17 expression on TNFα in collagen-induced arthritis (CIA). (
  • We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo . (
  • In current clinical trials, chimeric antibody-like receptors fused to signaling domains derived from TCR-ζ or Fc(ε)RIγ-chain are tested for their ability to lyse tumor cells in vivo. (
  • The direct clinical relevance of these findings is further underlined by the increased in vivo tumor rejection by T cells expressing chimeric receptors in presence of exogenous interleukin-2. (
  • These artificial receptors induced lysis of Ag-expressing target cells in vitro and in vivo. (
  • Because of the absence of sufficient interleukin-2 (IL-2) production by Fv-receptor triggered T cells, a supportive effect of exogenous IL-2 on the antitumor effect of these T cells can be demonstrated in a tumor animal model in vivo. (
  • Although CARs can trigger T cell activation in a manner similar to an endogenous T cell receptor, a major impediment to the clinical application of this technology to date has been the limited in vivo expansion of CAR + T cells, rapid disappearance of the cells after infusion, and disappointing clinical activity ( 4 , 6 ). (
  • Following T-cell engineering, resulting cells are expanded ex vivo with interleukin 2 (IL-2) before administration. (
  • In vitro Ls33 PGN induced IL-10-producing DCs able to achieve in vivo protection after adoptive transfer in a NOD2-dependent way. (
  • Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells. (
  • Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition. (
  • In addition, several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology. (
  • Res-TAMs largely correlated with tumor cell growth in vivo, while MoD-TAMs accumulation was associated with enhanced tumor spreading. (
  • Thus, rVV-HBZ induces a cytotoxic response against cells that express HBZ in vivo. (
  • CD4^+CD25^+ T cells isolated from peri-tumor regions of HCC displayed phenotype markers characteristic of regulatory T cells, and inhibited autologous CD8^+ cell proliferation. (
  • In light of this unexpected result, we reexamined the MHC class II requirement in the survival and lymphopenia-induced proliferation of CD4 + T cells. (
  • Coinjection of an excess of CD4 + or CD8 + T cells inhibits the proliferation of naive CD4 + T cells in these circumstances ( 14 , 23 ). (
  • These results suggest a role for intercellular competition in setting the threshold for naive T cell proliferation. (
  • Upon combined treatment, tumor cell proliferation was significantly decreased compared with single treated and untreated tumors. (
  • Taken together, our data show that peptide vaccination with cisplatin treatment leads to decreased tumor cell proliferation and TNFα-induced enhanced cisplatin-mediated killing of tumor cells, together resulting in superior tumor eradication. (
  • Influx of CD4 cells and gastritis are correlated with epithelial proliferation and apoptosis, and suggest that CD4-dependent H. pylori gastritis leads to epithelial damage with attendant proliferative and metaplastic responses. (
  • MicroRNA-21 (miR-21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c-kit + CSC remain unclear. (
  • Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. (
  • This immune complex-mediated vasculitis is characterized by a primary B-cell clonal proliferation accompanied by the deposition of immune complexes composed of complement factors, mono/oligoclonal IgMs with rheumatoid factor (RF) activity bound to oligo/polyclonal IgGs that, in the case of HCV infection, are mostly directed against HCV proteins [ 3 ]. (
  • As long as the fight against cancer remains an uphill battle, there will be an adamant drive for the development of aggressive therapeutics aimed at minimizing or inhibiting cancer cell proliferation and metastasis. (
  • For example, transferred macrophages induce proteinuria and mesangial cell proliferation in anti-GBM nephritis. (
  • As designed, the gene-modified Tandem T cells exhibit the new property of being resistant to AICD, showing instead an accelerated proliferation on tumor contact. (
  • IL-17 is a proinflammatory cytokine produced predominantly by T helper cells (Th17 cells) and, although there is controversy over the signals required for the differentiation of murine and human Th17 cells, both murine and human CD4 + Th17 T cells require IL-23 for their proliferation and maintenance ( 7 ). (
  • Proposed resistance mechanisms include T-cell exhaustion or immune tolerance, and selection for T cells with genetic alterations that increase proliferation and result in loss of the target antigen. (
  • These receptors cannot induce proliferation of resting T cells or trigger the production of optimal amounts of cytokines. (
  • 1997), FGF2 may participate in directing cell proliferation following pulmonary fibrosis. (
  • Still in question is whether the regrowth of functional insulin-producing cells occurs due to differentiation and proliferation of existing pancreatic stem cells, or whether the injected spleen cells re-differentiate to an insulin-producing form. (
  • In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. (
  • PD-L1-coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. (
  • We found that dacarbazine, temozolomide, and cisplatin induced expression of T-cell-attracting chemokines in several human melanoma cell lines in vitro . (
  • Development of thymic microenvironments in vitro is oxygen-dependent and requires permanent presence of T-cell progenitors. (
  • In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. (
  • These responses were mediated by CD4 + T cells, as shown by in vitro depletion of T-cell subsets. (
  • Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. (
  • In vitro, activation of IRF4 −/− CD4 + Th cells led to greatly increased apoptosis compared with wild-type cells. (
  • IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. (
  • IL-17 can also synergize with TNFα to induce cytokine and chemokine production by synovial fibroblasts and cartilage destruction in vitro and can promote osteoclastogenesis ( 1 , 5 , 6 ). (
  • For example, TNFα has been shown in vitro to drive the production of IL-17 by equipping DC with the ability to differentiate T cells toward a Th17 phenotype ( 11 ). (
  • Further, coculturing F5 TCR transduced T cells with human melanoma cell lines was sufficient to induce their dedifferentiation in vitro , inducing downregulation of MART1 and upregulation of NGFR. (
  • These CAR-T cells are then cultured in vitro into hundreds of millions of cells and finally infused back into the body of the patient. (
  • Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. (
  • In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. (
  • By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays. (
  • Here, using a genetically engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumor growth. (
  • On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. (
  • The tumor vasculature is involved in the preferential recruitment of other immune cells in place of effector T cells to the tumor microenvironment. (
  • Freund's complete adjuvant is effective in stimulating cell-mediated immunity and leads to potentiation of T helper cells that leads to the production of certain immunoglobulins and effector T cells. (
  • Whereas adaptive immune cells have rearranged receptor genes to recognize the universe of antigens, natural killer (NK) cells are innate immune lymphocytes with a limited repertoire of germ-line encoded receptors for target recognition. (
  • NK cells are innate lymphocytes capable of recognizing and killing target cells and producing immunoregulatory cytokines, especially IFN-γ ( 4 ). (
  • Unlike adaptive T and B lymphocytes, NK cells do not somatically rearrange their receptor genes, but rely upon a finite number of germ line-encoded inhibitory and activating NK receptors capable of recognizing MHC class I and class I-like molecules ( 8 , 9 ). (
  • Both CD4 + and CD8 + effector T (T eff ) lymphocytes directly engaged target cells. (
  • lead to initiation of autoantigen-specific responses in a cascade of molecular and cellular interactions between antigen-presenting cells and T lymphocytes. (
  • Certain types of vaccines, such as subunit proteins and whole or partially purified preparations of inactivated organisms, in general induce CD4 + T-cell responses but not CD8 + cytotoxic T lymphocytes (CTL). (
  • BACKGROUND: We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4(+) T lymphocytes in Brown Norway rats. (
  • Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. (
  • More than one-third of patients with metastatic uveal melanoma had objective tumor regression when treated with adoptive transfer of autologous tumor-infiltrating lymphocytes. (
  • For example, lymphocytes can be engineered to express T cell receptors (TCRs) that are specific for particular tumor antigens. (
  • This report describes the inability of Fv-ζ receptors to induce cytokine production in primary T lymphocytes. (
  • Most prominent among the cell types mediating dominant tolerance are the so-called regulatory T (T reg ) cells, a subset of CD4 + T lymphocytes critical for suppressing autoimmunity, tissue homeostasis, and uncontrolled immune response against pathogens. (
  • Potential therapeutic strategy - Inhibition of CCL2 nitration has been shown to enhance the accumulation of tumor-infiltrating lymphocytes (TILs) and improve efficacy of adoptive T cell therapy. (
  • As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. (
  • Despite the reduced absolute number of lymphocytes, the functional differentiation of T helper cells into Th1/17 cells and the production of autoantibodies were unimpaired. (
  • 4 , 6-8 Stroke-induced tissue destruction and disruption of the blood-brain barrier also result in the release of CNS autoantigens and their presentation to T-lymphocytes under proinflammatory immunogenic conditions. (
  • To address the possibility that C-Med 100[R] would influence the peripheral survival of lymphocytes, we performed adoptive transfer experiments. (
  • In fact, such harmless autoimmunity can be considered as physiologic since it is observed in all healthy individuals, both at the B cell level (natural autoantibodies) 1 and at the T cell level (one can derive MHC class II or organ specific T cell lines from normal peripheral blood lymphocytes) 2 Progression to pathogenic autoimmunity requires autoreactive B and/or T cell activation. (
  • Kinetic phases of distribution and tumor targeting by T cell receptor engineered lymphocytes inducing robust antitumor responses. (
  • A key issue in advancing the use of adoptive cell transfer (ACT) of T cell receptor (TCR) engineered lymphocytes for cancer therapy is demonstrating how TCR transgenic cells repopulate lymphopenic hosts and target tumors in an antigen-specific fashion. (
  • Strikingly, juxtaposed β cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. (
  • Cancer cells express antigens that elicit T cell-mediated responses, but these responses are limited during malignant progression by the development of immunosuppressive mechanisms in the tumor microenvironment that drive immune escape. (
  • A series of mechanisms prevent the recognition of tumor-associated antigens presented by tumor cells from activating a productive response able to clear transformed cells. (
  • Natural killer T (NKT) cells recognize glycolipid antigens presented by the MHC class I-related glycoprotein CD1d. (
  • The DNA vaccine protected the rats and led to a shift in the cytokine profile of T cells responding to disease target antigens from Th1 to Th2. (
  • Thus, CD25 DNA vaccination may induce protection from autoimmunity by inducing a cytokine shift in both the antiergotypic response and the response to the antigens targeted in the disease. (
  • Indeed, molecules expressed on activated T cells can serve as target antigens for the regulatory T cells called antiergotypic T cells. (
  • Cellular immune hyporesponsiveness can be induced by the presentation of soluble protein antigens to mucosal surfaces. (
  • The immune system can detect cancer cells in one of two ways: by recognizing molecules uniquely expressed in cancer cells (tumor-specific antigens or mutations) or by recognizing molecules that are differentially expressed in cancer cells relative to normal cells (tumor-associated antigens) [ 3 ]. (
  • A rational approach to build on the encouraging results in these two tumor systems (melanoma and renal cell carcinoma) would be to provide patient T cells the power to recognize tumor-associated antigens by design. (
  • Thus, the availability of T cells expressing TCRs that can bind tumor antigens with high affinity is naturally limited. (
  • recently developed a new strategy for generating T cells that can recognize tumors the same way they recognize viral or bacterial antigens. (
  • HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively) directed against HPV16 antigens. (
  • The HPV16-derived oncoproteins E6 and E7, responsible for both onset and maintenance of malignant transformation, are constitutively expressed in HPV induced cancers and represent non-self tumor-associated antigens. (
  • CD4 is an accessory molecule involved in the recognition of foreign antigens in association with MHC class II antigens by T cells. (
  • Autoimmune hemolytic anemia (AIHA) consists of loss of tolerance to self-antigens on red blood cells (RBCs) in the humoral compartment. (
  • 1 However, the frequency of AIHA grossly underestimates the frequency of humoral autoimmunity to RBC antigens, as many anti-RBC autoantibodies do not induce hemolysis, although the reasons for this are not known. (
  • The relative inefficiency of humoral tolerance to RBC antigens can not be predicted, given the known characteristics of central B-cell tolerance. (
  • Elimination of autoreactive thymocytes triggered by high-affinity interaction with self-antigens includes a class of cell-intrinsic mechanism referred to as recessive tolerance. (
  • In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. (
  • Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. (
  • In most cancers, tumor-specific antigens are not yet well defined, but in B cell malignancies, CD19 is an attractive tumor target. (
  • Our understanding of this process has been greatly enhanced by the discovery of several dozen tumor-associated antigens expressed by human melanoma, which can be recognized by tumor-reactive T cells. (
  • More detailed analyses of the T cell responses indicated that more than 60% of the persons with detectable ELISpot responses after vaccination exhibited CD8+ T cells to HIV antigens and approximately 40% exhibited CD4+ responses. (
  • The nature of vaccines (either humoral antibody immunity inducing or cell-mediated immunity inducing) depends on the location (extracellular or intracellular) and the expression of the antigens selected for incorporation. (
  • On the basis of these findings, these investigators have concluded that survival of peripheral CD4 + T cells did not depend on T cell antigen receptor (TCR) signaling induced by recognition of self-peptide/self-MHC molecule complexes. (
  • Ly49H is an NK cell-specific activating receptor that accounts for the genetic resistance to murine CMV (MCMV). (
  • These observations provide new insight into how activating receptor engagement shapes NK cell function and has important implications in how NK cells respond to tumors and during chronic viral infection. (
  • In general, NK cell activating receptors contain short cytoplasmic tails and require association with adaptor proteins to transduce signal once the receptor has been engaged. (
  • In CD4+ T cells, clonal anergy occurs when the T-cell receptor is activated in the absence of a costimulatory signal. (
  • When stimulated through engagement of their antigen receptor in the absence of costimulatory signals, CD4+ T cells become anergic to subsequent restimulations. (
  • T cell receptor (TCR) down‐modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. (
  • Although naturally occurring CD4 + CD25 + Tr cells are part of the normal T-cell repertoire, Tr1 cells are induced regulatory cells that can be generated from the peripheral naïve T-cell repertoire after activation via the T-cell receptor (TCR) and chronic exposure to antigen in the presence of exogenous IL-10 ( 5 ). (
  • Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4 −/− and IRF4 +/+ cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4 −/− CD4 + cells despite normal expression of the IL-4 receptor. (
  • Here, we evaluate orally administered selective tolllike receptor 7 agonists GS-986 and GS-9620 for their ability to induce transient viremia in simian immunodeficiency virus-infected rhesus monkeys on suppressive antiretroviral therapy. (
  • In an initial doseescalation study, and a subsequent dose-optimization study, we found that toll-like receptor 7 agonists activate multiple innate and adaptive immune cell populations in addition to inducing SIV RNA. (
  • In this review, we have described the characteristics of natural killer (NK) cells from multiple cell sources, including pluripotent stem cells, the chimeric antigen receptor (CAR)-modification method and strategy for these NK cells, and the current and planned clinical trials of CAR-modified induced pluripotent stem cell-derived NK cells. (
  • Sun C, Sun H, Zhang C, Tian Z. NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma. (
  • Chimeric antigen receptor T cells for sustained remissions in leukemia. (
  • Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. (
  • We also demonstrate that these regulatory T-cells with a pro-inflammatory T H 17-like phenotype can be reprogrammed to their "classical" anti-inflammatory phenotype by activating Toll-like receptor 2 (TLR2), which regulates the induction of cytotoxic T-lymphocyte-associated protein 4 (CTLA4). (
  • Truncated and substituted peptides, as well as bioinformatic analyses, were used to identify critical major histocompatibility complex (MHC)/T cell receptor (TCR) contact residues and the minimal core epitope. (
  • The progenitor first-generation immunoglobulin-T-cell receptor (IgTCR) that transmits Signal 1-only effectively mediated chimeric immune receptor (CIR)-directed cytotoxicity, but expressor T cells succumbed to activation-induced cell death (AICD). (
  • In chimeric receptor approaches, the receptors are MHC independent and the vector to modify autologous T cells is therefore an off-the-shelf reagent available to all patients irrespective of HLA-type. (
  • The success of autologous chimeric antigen receptor (CAR) T-cell therapy in patients with hematologic malignancies, particularly CD19 + B-cell acute lymphoblastic leukemia (B-ALL), has been partially mitigated by the development of severe side effects, such as neurotoxicity and cytokine release syndrome, in a subset of patients. (
  • This indicates that, unless an undiscovered second ligand for CD40 exists, T cells are capable of driving the inflammatory process by CD40-independent receptor:ligand and/or cytokine signaling. (
  • We report that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor ζ chain have potent non-cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL). (
  • A complex chemokine-chemokine receptor interaction is involved with immune cell migration to tumor microenvironment ( 7 ). (
  • Chimeric antigen receptor (CAR)- T cells are T cells which are genetically modified by the addition of tumor-reactive chimeric antigen receptors (CARs). (
  • 3D illustration of chimeric antigen receptor (CAR) T-cell therapy. (
  • The "oncoimmunotherapy wave" includes emerging check-pointinhibitor technology ( 3 ) as well as T-cell receptor (TCR) and CAR-T cell technologies (Figure 1). (
  • Pancreatic islets express high levels of IL-22 receptor and IL-22 has been shown to induce islet beta cell regeneration. (
  • Here, we describe a monoclonal CD8\(^+\) CD4\(^−\) αβ T cell receptor Vβ2\(^+\) CD28\(^+\) T cell lymphoma line, termed T8-28. (
  • 6 The viral envelope is required to bind to the cell receptor(s) and elicits both a humoral and a cellular immune response in infected individuals. (
  • As each B and T lymphocyte contains a unique antigenic receptor, it allows for a large and diverse population of cells capable of recognizing a wide spectrum of pathogens. (
  • One possibility is that pathophysiological stress, such as that induced by elevated IOP, triggers secondary immune or autoimmune responses, leading to RGC and axon damage after the initial insult is gone. (
  • Because the eye is an immune-privileged site, a critical question is how autoimmune responses, such as those against HSPs, are induced in glaucoma. (
  • NK cell responses are determined by signals received through activating and inhibitory cell surface receptors. (
  • NK cell effector responses include the release of cytokines and chemokines that shape the subsequent immune response as well as release of cytotoxic granules, which result in the destruction of the target cell. (
  • Enforced OX40 stimulation resulted in superior MCMV-specific CD4 + as CD8 + T cell responses when applied during booster SLP vaccination. (
  • IFN-γ + , TNF + , IL-2 + ) CD4 + and CD8 + T cell responses that were even higher in magnitude when compared to those induced by the virus, and this resulted in the best containment of virus dissemination. (
  • Our results show that the induction of strong T cell responses can be a fundamental component in the design of vaccines against persistent viral infections. (
  • CD4 + and CD8 + T cell responses play a critical role in controlling CMV infection in both mouse and human. (
  • During CMV infection, CD4 + and CD8 + T cell responses either follow the traditional course comprised by massive expansion followed by rapid contraction and maintenance at low levels or instead do not undergo contraction but remain at high frequency or even expand gradually. (
  • Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. (
  • The PD-1-PD-L1 pathway exerts its effects during the initial phase of activation and expansion of autoreactive T cells by attenuating self-reactive T cell responses during presentation of self-antigen by DCs. (
  • T-cell-adoptive therapies represent an attractive approach to treating cancers and have yielded some promising results in melanoma, even though complete clinical responses are only observed in a minority of patients ( 6 ). (
  • However, even when cancer vaccines induce immune responses in the majority of patients, only a few benefit from the treatment ( 8, 9 ). (
  • This continuing growth of tumors in the presence of functional antitumor immune responses, whether spontaneous or induced, is the most disturbing paradox of tumor immunology ( 10 ). (
  • Recent reports showed that immune responses in cancer patients are negatively regulated by immunosuppressive cells, mainly T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs), which suppress exuberant immune system activation and promote immunologic tolerance ( 3 , 4 ). (
  • NFAT1 deficiency blunted the induction of anergy in tumor antigen-specific CD4+ T cells, enhancing antitumor responses. (
  • Successful responses of the immune system against tumor cells are frequently hindered by the presence of an immunosuppressive tumor microenvironment ( 1 ). (
  • However, despite activating T cells against AQP4, these rat and mouse models do not develop a clinical neurological phenotype either because pathogenic T cells responses are limited by a combination of central and peripheral tolerance or because certain AQP4 epitopes are not pathogenic. (
  • Furthermore, γ-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. (
  • This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4 + and CD8 + , and with early influenza virus-specific cytotoxic T-cell responses. (
  • Therefore, cross-protective immunity induced by vaccination with γ-irradiated influenza A virus is mediated mainly by Tc-cell responses. (
  • Natural infections with influenza A viruses induce immune responses that provide protection against not only homologous but also heterosubtypic influenza A viruses ( 14 , 16 , 26 , 37 , 45 , 57 ). (
  • Therefore, it appears that heterosubtypic immunity induced by live influenza virus is a multifaceted phenomenon that involves not only the Tc-cell response but also other responses. (
  • Considering the negligible heterosubtypic immunity induced by current inactivated influenza vaccines, which induce strain-specific antibody responses, further investigation is required to generate a vaccine with a capacity to induce cross-protective immunity. (
  • In contrast, live attenuated organisms and subunit proteins formulated with certain experimental adjuvants can induce both types of responses. (
  • DNA vaccines) has shown promise as a viable means of inducing broad-spectrum T-cell responses. (
  • Cancer immunotherapeutic approaches induce tumor-specific immune responses, in particular CTL responses, in many patients treated. (
  • Recently there has been a growing interest in the induction of T regulatory (Tr) cells as a strategy to modulate undesired immune responses and achieve graft-specific tolerance (rev. in 2 ). (
  • Adoptively transferred late allergic airway responses are associated with Th2-type cytokines in the rat. (
  • Late allergic airway responses can be transferred by CD4+ T cells in the rat. (
  • To investigate the role of T-cell cytokines in these responses, we examined the expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. (
  • Recent studies have shown that adoptive T-cell therapy led to salvage responses in a variety of refractory solid tumors. (
  • 1998) IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma. (
  • Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory T H 17-like phenotype. (
  • Adequate clearance of A. fumigatus relies on T-helper cell-mediated pro-inflammatory immune responses, and particularly the T-helper (T H )1 response 8 - 11 . (
  • Tissue-resident memory T (T RM ) cells have been implicated in protective immune responses against viral infections, but the role of T RM cells following mycobacterial infection is unknown. (
  • However, this recognition was imperfect, or the tumor would have regressed on its own, and the degree and durability of the responses were infrequently satisfactory, whether due to induced tolerance or antigen modulation. (
  • NY-ESO-1 is an immunogenic tumor antigen that is highly expressed in cancers such as melanoma and synovial sarcoma, and NY-ESO-1 + autologous T-cell therapy has previously been shown to produce objective responses in 11 of 18 patients with synovial sarcoma. (
  • Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. (
  • This is not surprising because CD40:CD40L interactions are known to play many roles in cell-mediated inflammatory responses, including stimulation of expression of adhesion and homing molecules on vascular endothelium, stimulation of chemokine and inflammatory cytokine production, stimulation of the production of IL-12, which is critical for maturation of the inflammatory Th1 subset, and stimulation of fibroblasts (105) ( Table 1 ). (
  • CAR-mediated T cell responses may be further enhanced with addition of costimulatory domains. (
  • However, these therapies often result in only partial responses to treatment, allowing some cancer cells to survive and become fully resistant to therapy. (
  • CAFs, which can be identified by expression of the membrane protein Fibroblast Activation Protein alpha/FAP , suppress anti-tumor immune responses by restricting T cells to the stroma and preventing them from accumulating in the vicinity of cancer cells by at least two mechanisms. (
  • Regulatory T cells (Treg) play an important role in the maintenance of peripheral tolerance and the modulation of immune responses against infections and tumor cells. (
  • Recruitment of Tregs favors tumor progression and depletion of these cells enhances antitumor immune responses ( 2-6 ). (
  • We hypothesize that antiviral immune responses generated during oncoviral therapy assist the immune system in overcoming the immune evasive strategies used by tumors and induce antitumor immune responses. (
  • 4 , 6 , 9 It has, therefore, been suggested that stroke-induced immunosuppression protects from stroke-induced autoimmune responses against CNS autoantigens. (
  • In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mm Hg females). (
  • Activated PIK3CD drives innate B cell expansion yet limits B cell-intrinsic immune responses. (
  • Adoptive transfer of immune T cells also conferred protection in the challenge model whereas passive transfer of immune serum did not, indicating the critical role for T cell responses in control of this infection. (
  • These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance. (
  • Therefore, identifying drugs that favor T-cell trafficking to the tumors is essential to improve cancer vaccines. (
  • Therefore, we sought to understand the signals responsible for T-cell trafficking to cutaneous tumors in melanoma and to determine whether they are altered by chemotherapy. (
  • Tumor-bearing animals mount a strong antitumor T-cell response, but although this response controls the outgrowth of visceral metastases, they have no effect on cutaneous tumors. (
  • Using global transcriptome analysis, we also analyzed cutaneous metastases resected from patients with melanoma before and after chemotherapy and found increased T-cell infiltration into the chemotherapy-sensitive tumors ( 19 ). (
  • The aim of this study is to identify molecular cues controlling T-cell infiltration into cutaneous tumors and to find treatments promoting T-cell infiltration. (
  • Upon SLP vaccination, tumors were highly infiltrated with HPV-specific, tumor necrosis factor-α (TNFα)- and interferon-γ (IFNγ)-producing T cells. (
  • We set out to investigate one possible explanation for the failure of CTLs to eliminate tumors, specifically, the concept that this failure is not dependent on inhibition of T cell function. (
  • In a mouse model of tumor-associated inflammation in which the antitumor effects of antigen-specific CTLs are eradicated by expression of IL-1β in the tumor cells, we determined that therapeutic failure was not caused by more profound suppression of CTLs by IL-1β-expressing tumors than tumors not expressing this proinflammatory cytokine. (
  • Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. (
  • Evaluation of diseased tissue from patients with diffuse large B cell lymphoma revealed that IL-6 expression is enhanced in tumors that lack CD37 expression, and patients with CD37-deficent tumors exhibited worse overall survival than patients with CD37-expressing tumors. (
  • When expressed by gene therapy techniques in recipient T cells, the resulting designer T cells are redirected by the neo-specificity of the CIR to attack tumors expressing the surface antigen recognized by the immunoglobulin. (
  • There is compelling evidence that CD8 + cytotoxic T cells are crucial players in the protective immune response against viral infections and tumors ( 4 ). (
  • Immunosuppression - CD8+ T cells undergo Fas Ligand -mediated apoptosis in tumors with high levels of Fas Ligand. (
  • Clinical studies are ongoing to evaluate the efficacy of these cells in solid tumors. (
  • For example, melanomas and other tumors induce lymphangiogenesis with a protein called Vascular Endothelial Growth Factor C (VEGF-C). The presence of VEGF-C and subsequent lymphangiogenesis are generally signs of metastasis and create a poor prognosis for the patient. (
  • This not only resulted in eradication of the primary tumors, it also encouraged T cell infiltration into metastatic tumors and resulted in long-term protection. (
  • For example, the FDA recently approved CAR-T cell therapy for leukemia and several checkpoint inhibitors are already approved for the treatment of solid tumors such as melanoma. (
  • After an initial brief stage of systemic distribution, TCR-redirected and genetically labeled T cells demonstrated an early pattern of specific distribution to antigen-matched tumors and locoregional lymph nodes, followed by a more promiscuous distribution 1 wk later with additional accumulation in antigen-mismatched tumors. (
  • We also studied the regulatory properties of other cytokines, separately or together with TGF-β, on CD4^+CD25^+ T cells generated by allo-stimulation. (
  • NK cells also produce cytokines such as IFN-gamma (IFN-γ) to protect the host during the innate response to infection. (
  • Research has shown that cancer cells consistently induce local immunosuppression and then create systemic immunosuppression via immune-suppressive cells and cytokines ( 2 ). (
  • Specifically, in a murine model of melanoma, we found that cancer cells induced anergy in antigen-specific CD4+ T-cell populations, resulting in defective production of several key effector cytokines. (
  • The specific T cells involved in conferring immunity can include both CD4 + and CD8 + T cells, often through the action of secreted cytokines and cytolytic activity, respectively. (
  • The main cytokines produced by Tr1 cells are IL-10 and transforming growth factor-β (TGF-β) in the absence of significant levels of IL-2 or IL-4 ( 6 ). (
  • We found that IL-4-induced innate CD8+ T cells immediately accumulated after viral infection and produced a robust amount of effector cytokines. (
  • CNS-produced cytokines may drive CAR T cell-associated neurotoxicity independently of CAR T cells. (
  • CAR T cell-induced neurotoxicity is associated with elevated inflammatory cytokines and BBB disruption. (
  • Although deleterious effects of proinflammatory cytokines are well characterized, direct cytotoxic effects of invading immune cells on the ischemic brain and the importance of their antigen-dependent activation are essentially unknown. (
  • Therefore, adoptive T-cell therapy using primary T cells transfected with single chain receptors might benefit substantially from the accompanying administration of cytokines. (
  • 2015), mesenchymal stem cells (MSCs) and FGF2 synergistically reduced the level of inflammatory cytokines in the treatment of LPS-induced lung injury. (
  • CAR-T cells can lead to the massive and rapid release of cytokines into the blood, which may cause a sudden drop in the blood pressure, and dangerously high fever. (
  • In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. (
  • In addition to the many roles of T cell-derived cytokines in differentially modulating these diverse macrophage activities, research over the last few years has demonstrated that contact-dependent signaling which occurs during T cell-macrophage adhesion is a critical triggering event in the activation of macrophage function. (
  • Renal tissue macrophages, T cells, and neutrophils produce various reactive oxygen species, proinflammatory cytokines, metalloproteinases, and growth factors, which modulate the local response and increase inflammation within the diabetic kidney. (
  • We confirmed that naive CD4^+ cells stimulated with alloantigens in the presence of TGF-β(transforming growth factor-β) differentiate into suppressor cells with a phenotype and functional properties similar if not identical with natural regulatory CD4^+CD25^+ T cells. (
  • Although it has been reported that CD4^+ cells become regulatory T cells ('Tr1 cells') when repeatedly stimulated with IL-10,IL-10 inhibited CD25 expression on CD4^+* cells. (
  • Thus, the gut environment favours the generation of autoreactive CD4 + T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity. (
  • However, inflammatory T H 17 cells can acquire a regulatory phenotype after being recruited into the small intestine, as demonstrated in a model of systemic tolerance induced by anti-CD3 antibody 14 . (
  • Therefore, the gut and gut-associated lymphoid system are probable sites for functional maturation of autoimmune pathogenic T cells and regulatory T cells capable of suppressing autoimmune inflammation outside the gut. (
  • Both the programmed death (PD) 1-PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. (
  • Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. (
  • Induction of regulatory CD8 γδ T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM. (
  • One solution to this problem is the induction of transplantation tolerance mediated by T regulatory cells. (
  • T regulatory type 1 (Tr1) cells are characterized by their production of high levels of interleukin (IL)-10, which is crucial for their differentiation and suppressive function. (
  • The Costimulatory Pathways and T Regulatory Cells in Ischemia-Reperfusion Injury: A Strong Arm in the Inflammatory Response? (
  • It is self-evident that both outcomes could be beneficial in type 1 diabetes ( Fig. 1 ) where there may be both a regulatory T-cell (Treg) defect and effector cells that are relatively resistant to regulation ( 7 ). (
  • ASI has two predominant beneficial effects, namely deletion of T-cells and induction of regulation, either via priming of regulatory T-cells (Tregs) or immune deviation. (
  • Our study demonstrates that Aspergillus fumigatus induces regulatory T-cells with a T H 17-like phenotype. (
  • Similarly, soluble CTLA4 could reverse the pro-inflammatory phenotype of Aspergillus- induced regulatory T-cells. (
  • In conclusion, our results suggest a role for regulatory T-cells with a pro-inflammatory T H 17-like phenotype in Aspergillus -associated immunopathology, and identifies key players, i.e. (
  • Whereas airway-resident memory CD4 + T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8 + T cells displayed prototypical T RM features. (
  • IL-10 and natural regulatory T cells: two independent anti-inflammatory mechanisms in herpes simplex virus-induced ocular immunopathology. (
  • Two prominent anti-inflammatory mechanisms involved in controlling HSV-1-induced corneal immunopathology (stromal keratitis or SK) are the production of the cytokine IL-10 and the activity of natural regulatory T cells (nTregs). (
  • Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis. (
  • Foxp3 and its protein partners establish a regulatory T (T reg ) cell transcription profile and promote immunological tolerance. (
  • In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. (
  • The functions of T effector cells and T regulatory cells (Tregs) were compared between treated and nontreated groups. (
  • Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. (
  • Depletion experiments showed that regulatory T cells were dispensable for the protective effect of MCAO. (
  • The development of regulatory T cells was investigated by following the expansion of CD4 + FoxP3 + cells. (
  • In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. (
  • Repeated intraportal donor specific transfusion may induce tolerance following adult living related donor liver transplantation. (
  • PD-1 genotype of the donor is associated with acute graft-versus-host disease after HLA-identical sibling donor stem cell transplantation. (
  • T Cell Cosignaling Molecules in Transplantation. (
  • NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. (
  • Phase II study of haploidentical natural killer cell infusion for treatment of relapsed or persistent myeloid malignancies following allogeneic hematopoietic cell transplantation. (
  • 5 Department of Blood and Marrow Transplantation, Institute for Stem Cell Biology and Regenerative Medicine, and Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. (
  • Graft versus host disease (GvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation and is the main cause of transplant-related mortality. (
  • Hematopoietic stem cell transplantation (HSCT) has become an accepted and widely used treatment option for defined malignant and nonmalignant diseases. (
  • Tolerance induction by adoptive transfer of FLDCs could be a useful approach for promoting graft acceptance after organ transplantation. (
  • Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). (
  • Dietary fatty acids also influence gut T-cell differentiation and EAE disease course 4 . (
  • It is generally known that rapid generation of IL-4 supports the crucial Ag-specific Th2 cell differentiation. (
  • IL-23 is a heterodimeric protein composed of a p19 subunit and a p40 subunit, whereas IL-12, an important cytokine for Th1 cell differentiation, is formed when the p40 subunit dimerizes with p35 ( 8 ). (
  • Cartilage rings contribute to the proper embryonic tracheal epithelial differentiation, metabolism, and expression of inflammatory genes Am J Physiol Lung Cell Mol Physiol. (
  • Inflammation-induced differentiation may be a mechanism of resistance to adoptive T-cell therapies. (
  • reported a storage T-cell subset, known to as control cell storage Testosterone levels (TSCM) cells, possessing long-living capability, self-renewal, and multi-differentiation into TCM, TEM, and effector Testosterone levels (Teff) cells.5 TSCM are defined by naive gun memory and CD45RA+CD62L+CCR7+ gun CD95+ and classified between naive and TCM cells. (
  • Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated neurotoxicity in experimental stroke. (
  • Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8 + T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. (
  • The development of a cell-mediated response is currently hypothesized to depend on the differentiation of interferon (IFN)-gamma producing Th1 cells from activated Th0 precursors (10,11). (
  • Acute depletion of CD4 + or CD8 + T-cell subsets in these knockout animals, but not in their wild-type counterparts, abrogated heterosubtypic protection ( 8 ). (
  • To date, several host- and virus-related factors have been implicated in the progression to MCII, such as the virus-induced expansion of selected subsets of B-cell clones expressing discrete immunoglobulin variable (IgV) gene subfamilies, the involvement of complement factors and the specific role of some HCV proteins. (
  • Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. (
  • further, long-term persistent T cells were derived from all T-cell subsets (from naïve to differentiated memory T cells) and enriched for memory T cells. (
  • effector storage (TEM) cell subsets with the capability to efflux medications and survive publicity to chemotherapy.4 Gattinoni et?al. (
  • Different T cell subsets in the nodule and synovial membraneAbsence of interleukin-17A in rheumatoid nodules. (
  • Both cell subsets were depleted after chemotherapy, but MoD-TAMs rapidly recovered and performed phagocytosis-mediated tumor clearance. (
  • Chronic exposure of Ly49H with m157, however, induces tolerance in these same cells. (
  • PD-1-PD-L interactions regulate peripheral CD4 and CD8 T cell tolerance at multiple checkpoints. (
  • T reg cells are also essential for the maintenance of peripheral tolerance, and roles for B7-CD28 family members during T reg cell development are emerging. (
  • This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings. (
  • However, the mechanisms of remote tumor cell-induced organ tolerance still require further clarification. (
  • T-cell hyporesponsiveness can be caused by clonal anergy or adaptive tolerance, but the pathophysiological roles of these processes in specific tumor contexts has yet to be understood. (
  • One of the effects reported to occur in the tumor microenvironment is the induction of antigen-specific tolerance in CD4+ and CD8+ T cells ( 6, 7 ). (
  • IL-2 promotes either immunity or tolerance in a concentration dependent fashion by acting on T helper cells, CTL and NK cells. (
  • Central tolerance in the Bcell compartment occurs as a result of exposure to autoantigens at several checkpoints during B-cell development. (
  • An additional layer of control of overexuberant immune response is mediated by specialized classes of immune cell types that contribute toward an essential trans-acting mechanism termed dominant tolerance. (
  • The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. (
  • For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. (
  • For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. (
  • Induction of Tolerance by Adoptive Transfer of Treg Cells. (
  • This effect was mediated by TNFα released by T cells, and TNFα alone was sufficient to induce reversible dedifferentiation of melanoma cells. (
  • Chemotherapy acts, in part, by direct induction of apoptosis in cancer cells. (
  • Thus, we hypothesized that miR-21 reduces hydrogen peroxide- (H 2 O 2 -) induced apoptosis in c-kit + CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. (
  • miR-21 mimics efficiently reduced H 2 O 2 -induced apoptosis in c-kit + CSC, as evidenced by the downregulation of the proapoptosis proteins caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2. (
  • Taken together, these results indicate that the anti-H 2 O 2 -induced apoptosis effect of miR-21 in c-kit + CSC is contributed by PTEN/PI3K/Akt signaling. (
  • Here, we show that CD4 + T helper (Th) cells lacking IRF4 (IRF4 −/− ) are highly sensitive to apoptosis. (
  • Coculture of IRF4 −/− and IRF4 +/+ CD4 + cells did not increase survival of IRF4 −/− CD4 + cells, indicating that the enhanced rate of IRF4 −/− Th cell apoptosis was neither transferable nor due to lack of a cytokine. (
  • Enhanced CD4 + cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. (
  • Also, these CD8(+) T cells functioned by releasing inflammatory IFNγ and TNFα in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. (
  • Here, we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells. (
  • WNV replication decreased cell viability and induced apoptosis as indicated by the activation of the effector caspase-3, the initiator caspases-8 and -9, poly(ADP-ribose)polymerase (PARP) cleavage and the release of cytochrome c from the mitochondria. (
  • Inhibition of the caspases-8 or -9 inhibited PARP cleavage, demonstrating that both caspases are involved in WNV-induced apoptosis. (
  • Pan-caspase inhibition prevented WNV-induced apoptosis without affecting virus replication. (
  • We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. (
  • Here, we used human glioma cell line T98G that is highly susceptible to WNV-induced apoptosis to investigate the contribution of caspase-dependent apoptosis to WNV infection-induced cell death. (
  • In each passive transfer study, the anti-AQP4 antibody was only pathogenic in the context of a T-cell based autoimmune attack on the central nervous system. (
  • These findings reveal a novel mechanism for suppressing cell-mediated autoimmune disease. (
  • Insulin-dependent diabetes mellitus (IDDM) 1 results from the selective destruction of insulin-producing β cells in the islets of the pancreas, within an autoimmune inflammatory "insulitis" lesion ( 1 , 2 ). (
  • It has been suggested that whole cell pertussis vaccine can have an adjuvant effect leading to an autoimmune process and β cell damage. (
  • However, not surprisingly, a reduction in MCII symptoms was shown also after anti-B-cell treatment (e.g. rituximab) suggesting a concomitant role of the pathogen and the host in the establishment of this autoimmune disorder [ 5 ]. (
  • As the autoreactive T cells are present but non-responsive, these data indicate that factors that reverse T-cell non-responsiveness may be central to the pathogenesis of autoimmune hemolytic anemia. (
  • It has also been investigated in an animal model of Parkinson's disease, or as well used in emulsion with Myelin oligodendrocyte glycoprotein (MOG), a peptide inducing Experimental autoimmune encephalomyelitis (EAE) in animal studies for efficacy testing of multiple sclerosis treatments. (
  • FCA is known to stimulate production of tumor necrosis factor, which is thought to kill the T-cells responsible for the autoimmune destruction of the pancreatic beta cells. (
  • In the following sections, we try to provide a succinct account of T cell signaling of macrophages which, although brief and simplified for the sake of clarity, emphasizes the complexity of the cascading cell-cell interactions involved in a relapsing inflammatory autoimmune disease. (
  • 3 The question is thus posed of the origin and the modalities of such activation of autoreactive B or T cells in spontaneously occurring autoimmune diseases. (
  • The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. (
  • Depletion of CTLs decreased infarct volumes and behavioral deficit in two ischemia models, whereas NK cell depletion had no effect. (
  • T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8(+) T cells conferred to the protective efficacy in a dose-dependent way. (
  • Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. (
  • Here, we show that SLP vaccination can be safely combined with seven relevant chemotherapeutics without hampering the vaccine-induced antitumor response. (
  • In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and T RM cells in the lung, as defined by surface marker phenotype. (
  • Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. (
  • Hence, the goal of vaccination is to enhance the number of antigen-specific B and T cells against a given pathogen. (
  • antigen‐specific inflammatory arthritis and a T cell‐derived lymphoma. (
  • The relapsed tumor exhibited increased CD8 + cytotoxic T-lymphocyte infiltration, consistent with increased inflammatory signals in the tumor microenvironment, and expression of inflammation-induced dedifferentiation markers including NGFR was increased. (
  • Macrophages play diverse roles in episodic T cell-mediated inflammatory diseases such as multiple sclerosis and rheumatoid arthritis, function as accessory cells for T cell activation, as pro-inflammatory cells, as effector cells which mediate tissue damage, and as anti-inflammatory cells which promote wound healing. (
  • This is a brief review of the rapidly expanding, but still incomplete, knowledge of how T cells, through both contact-dependent and cytokine signals, regulate macrophage function during inflammatory disease. (
  • Research over the past decade has only begun to unravel the complex interactions between T cells and macrophages that are involved in the pathogenesis of cell-mediated inflammatory diseases such as multiple sclerosis. (
  • The types of cells present reflect the state of progression of the inflammatory lesion. (
  • Macrophages play critical accessory, inflammatory, and effector roles in this non-septic T cell-mediated inflammatory disease (5-9) and tend to be present throughout the inflammatory process. (
  • Upon maturation, these Th1 cells, as well as inflammatory CD8+ cells, both of which produce IFN-gamma and tumor necrosis factor (TNF)-alpha/beta, play a dominant role in macrophage activation and pathogenesis of the inflammatory lesion (1,3,12-15). (
  • In contrast, IL4/IL10-producing T cells are hypothesized to play a role in down-regulation of the inflammatory response (1,3,16). (
  • This view is changing now because there is a growing body of evidence implicating inflammatory cells at every stage of diabetic nephropathy. (
  • However, recent studies suggest that inflammatory processes and immune cells might be involved in the development and progression of DN. (
  • Some of the transferred cells even strongly expand and convert to an effector-like phenotype. (
  • Several mechanisms have been proposed to account for the anergic phenotype of tumor antigen-specific T cells. (
  • Animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that specific targeting of AQP4 is essential for this phenotype. (
  • Innate T cells are heterogeneous population of T cells that acquire effector/memory phenotype as a result of their maturation process in thymus, unlike conventional T cells that differentiate into memory cells after antigen encounter in periphery. (
  • In this chapter, data will be reviewed that indicate that such mechanisms essentially involve CD4 T cells which begin to be characterized in terms of their phenotype, their autoantigen specificity, their mode of action, their genetic control and their sensitivity to environmental factors. (
  • The role of G-MSCs in controlling the development and severity of CIA mostly depends on CD39/CD73 signals and partially depends on the induction of CD4+CD39+FoxP3+ Treg cells. (
  • PD-L1 −/− antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. (
  • These data identify the induction of intratumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with antitumor activity. (
  • The role of hepatitis C virus (HCV) infection in the induction of type II mixed cryoglobulinemia (MCII) and the possible establishment of related lymphoproliferative disorders, such as B-cell non-Hodgkin lymphoma (B-NHL), is well ascertained. (
  • The major benefit of Treg induction is linked suppression, the process by which Tregs induced to regulate in response to one autoantigen (e.g. (
  • Induction of memory T cells has been shown to be essential for protective TB vaccines. (
  • antibody blockade of CD40:CD40L interactions completely blocks T cell contact-induction of CD80 expression (25). (
  • R16-specific T cells from treated tEAU rats into naïve recipients prevented induction of tEAU by R16-specific T cells from nontreated tEAU rats. (
  • To be effective, stroke had to be induced during the induction phase or the early clinical stage of arthritis. (
  • This is related to the induction of Th17 cells by adjuvant treatment and these cells produce Interleukin-22 (IL-22). (
  • We have previously discovered that inflammation-induced changes in the neuronal membrane play a key role in the induction of axon degeneration. (
  • In this student project we want to set up a cell culture model that allows us to study the induction (and ultimately the therapeutic prevention) of such membrane changes in a simplified model. (
  • The so far limited success of therapeutic cancer vaccines is largely due to our incomplete understanding of the mechanisms preventing the action of T cells locally. (
  • Strategies to enhance cell survival after adoptive transfer would produce notable therapeutic implications in post-MI patients. (
  • More recently, three distinct therapeutic modalities have revolutionized the field of immunooncology: checkpoint inhibitors, adoptive T cell transfer, and bivalent antibodies. (
  • Enhanced, autocrine IL-6 signaling has been observed in B lymphoma cells from patients, and therapeutic approaches targeting the IL-6 pathway are currently under investigation. (
  • Together, this study identifies CD37 as a tumor suppressor that directly protects against B cell lymphomagenesis and provides a strong rationale for blocking the IL-6 pathway in patients with CD37 - B cell malignancies as a possible therapeutic intervention. (
  • Miltenyi Biotec as the manufacturer of the CliniMACS System does not give any recommendations regarding the use of separated cells for therapeutic purposes and does not make any claims regarding a clinical benefit. (
  • The potential clinical efficacy of therapeutic strategies that target T cell exclusion mechanisms also needs to be assessed. (
  • Potential therapeutic strategy - Both collagenase and CCL5 have been shown to increase T cell movement out of stromal regions and into the vicinity of cancer cells. (
  • Potential therapeutic strategy - CXCR4 inhibitors increase T cell numbers in the vicinity of cancer cells and improve efficacy of anti-PD-L1 antibody treatment. (
  • Potential therapeutic strategy - Treatment with EDNRB/ET B R inhibitors inhibitors inhibitors increased T cell adhesion to endothelial cells, which resulted in elevated TILs and an anti-tumor response to an otherwise ineffective anticancer vaccine. (
  • Thus, FGF2 plays a critical role in preventing IAV-induced lung injury, and FGF2 is a promising potential therapeutic target during IAV infection. (
  • These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy. (
  • Reovirus, a naturally occurring benign human pathogen, preferentially targets cancerous cells of many origins and is currently under clinical trials as a novel anticancer therapeutic agent ( 23 , 24 ). (
  • Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. (
  • Engagement of self-MHC class I by inhibitory NK receptors prevents NK cell killing of normal cells, and NK cell activity is dictated by a complex integration of signals from both inhibitory and activating NK receptors ( 10 ). (
  • Using activating and inhibitory receptors expressed on their cell surface, NK cells distinguish normal "self" cells from abnormal cells by scanning the molecules expressed on the cell surface of potential target cells. (
  • During times of stress and/or infection, host cells can over express certain endogenous self-ligands, which can be recognized by specific activating receptors expressed on the NK cell. (
  • In addition to activating receptors that recognize "induced-self" molecules, NK cells express activating receptors that recognize non-self molecules. (
  • Thus, NK cell activating receptors can recognize both self and non-self ligands. (
  • Ligation of inhibitory receptors and defective activation of antigen presenting cells, among others, seem to contribute to the establishment of a hyporesponsive state in tumor specific T cells ( 3 , 8 ). (
  • Protective antiergotypic T cells were found in both the CD4 + and CD8 + populations and expressed α/β or γ/δ T cell receptors. (
  • T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. (
  • Such therapies applying chimeric immune receptors (CIR) have been variously termed T-bodies, universal receptors, or designer T cells (reviewed in ref. 2 ). (
  • However, if these receptors are confirmed to be safe, this approach could not only increase the effectiveness of adoptive T cell therapy, but substantially speed up the development of libraries of TCRs that recognize a wide range of cancer types. (
  • Chimeric receptors with extracellular antibody-binding domains (Fv) connected to signaling portions of TCR-ζ 1 2 or Fc(ε)RIγ-chain 2 enable T cells to recognize native antigen (Ag). (
  • 2-10 The ultimate goal is to transfect primary T cells from cancer patients with tumor antigen-specific Fv-receptors for use in adoptive transfers. (
  • 10 11 Despite TCR/CD3-like signaling capacities of Fv-ζ receptors in T-cell hybridomas, clones, and activated T cells, 1 2 these receptors were not sufficient to activate resting primary T cells. (
  • His laboratory efforts have concentrated on the development of novel antigen receptors for T-cells with optimized specificity and efficacy in treating cancers. (
  • T cells are separated from other cells from the patient's own peripheral blood, and are genetically modified using a disarmed virus to produce surface receptors called CARs. (
  • The receptors on their surface guide these cells to recognize and kill cancer cells. (
  • We found that treatment of murine alio-activated CD4^+ T cells with TGF-β and IL-2 also enhanced expression of CD25 and enabled these cells to develop potent suppressive activity. (
  • IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer. (
  • Preclinical validation of candidate constructs will be performed using murine models of adoptive cell transfer. (
  • HealthDay News - Induced pluripotent stem cell (iPSC) vaccines prevent tumor growth in syngeneic murine cancer models in a prophylactic setting, according to a study published online February 15 in Cell Stem Cell . (
  • Indeed, defects in innate immunity, including natural killer (NK) cells, often lead to uncontrolled, fatal infections ( 1 ⇓ - 3 ). (
  • Several processes have been described to contribute to the immune escape that allows tumor cells to block antitumor immunity including, among others, the downregulation of antigen presentation by tumor cells and the expression of suppressor factors or the recruitment of cells with suppressor activity ( 1-5 ). (
  • Despite these observations, the immunological basis of heterosubtypic immunity against influenza A virus infection and the contribution of the Tc-cell response remain important areas of research. (
  • This is largely due to their ability to induce only humoral immunity ( 9 ). (
  • However, recent studies have suggested that inactivated influenza viruses administered intranasally (i.n.) may elicit B-cell-dependent cross-protective immunity ( 18 , 41 , 49 , 50 , 55 ). (
  • However, in only a few instances has the nature of the effector cells responsible for protective immunity been described ( 7 , 16 ). (
  • Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. (
  • Importantly, repeated DNA vaccinations, a major advantage over live-vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1(+) and Tim-3(+) CD8(+) T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8(+) T cells inversely correlating with tumor mass. (
  • These immunologic abnormalities associated with the tumor microenvironment either inhibit the priming of antitumor adaptive immunity ( 1 ) or tolerize tumor-specific CD4 ( 13 , 14 ) and CD8 ( 15 , 16 ) T cells. (
  • While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. (
  • Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. (
  • We have previously shown that Tregs CD4 + CD25 + Foxp3 + are involved with mouse squamous cell carcinoma (SCC) development ( 5 ). (
  • Although the proportion of CD4^+CD25^+ T cells in the liver was lower than in the peripheral blood, we found a significant increase of CD4^+CD25^+ T cells in the marginal regions of hepatocellular carcinoma(HCC), but not in unaffected areas of the liver. (
  • During the past two decades, peripheral T cell homeostasis has been studied extensively. (
  • Together with thymic generation, such interactions would regulate the size of the peripheral T cell pool. (
  • Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells. (
  • In addition, one should expect interindividual variations in the autoreactive repertoire of T-cells: some islet-reactive T-cells might already be activated at the time of immunization and their avidities can be expected to vary depending on central (thymic) and peripheral tuning events, which in turn will influence the character (magnitude and cytokine production) of the resulting antigen-specific response. (
  • NY-ESO-1 c259 cells were identified in the peripheral blood 6 months post-infusion. (
  • Bloodstream and cells examples Peripheral bloodstream (PB) was acquired from healthful volunteer contributor and from malignancy individuals and tonsils had been acquired Golvatinib from chronic tonsillitis or rest apnea symptoms individuals. (
  • However, whether this failure is central versus peripheral and at the level of T and/or B cells remains unresolved. (
  • These studies demonstrated detectable T cell immunogenicity as measured by the ELISpot assay in about 80% of recipients with a median magnitude in the range 275-300 spot forming units (SFU)/million peripheral blood mononuclear cells (PBMC), a frequency and magnitude greater than any other T cell-based approach at the time of the initiation of the Step trial in 2005 [4] . (
  • For both adoptive transfer systems, at 36 hr posttransfer, cells from blood, peripheral lymph nodes, and spleen were harvested from a subset of recipients, and the remainder of recipients were infected with IAV. (
  • In patients with melanoma, these chemokines were also upregulated in chemotherapy-sensitive lesions following chemotherapy, and correlated with T-cell infiltration, tumor control, and patient survival. (
  • Therefore, with this study, Chandran and colleagues tested whether adoptive transfer of TILs could mediate tumor regression in uveal melanoma. (
  • 1995) A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin's lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. (
  • Phase II clinical trials demonstrated that 9 patients (7%) with metastatic melanoma and 10 patients (7%) with metastatic renal cell cancer treated with biologic therapy of HD IL-2 achieved complete regression of disease with hypotension, secondary to underlying capillary leak, being the most commonly reported toxicity [ 7 - 9 ]. (
  • Adoptive transfer of MART1-specific T cells induced tumor regression in a patient with melanoma. (
  • This case study demonstrates that inflammation-induced dedifferentiation of tumor cells may promote resistance to ACT in patients with melanoma. (
  • Dr. Yang has been involved in the clinical and scientific study of T-cell adoptive therapy and other immunotherapies to treat melanoma and other cancers. (
  • Thrombotic microangiopathy in metastatic melanoma patients treated with adoptive cell therapy and total body irradiation. (
  • The iPSC vaccine inhibited melanoma recurrence at the resection site as an adjuvant and reduced metastatic tumor load, which was correlated with fewer Th17 cells and increased CD11b + GR1 hi myeloid cells. (
  • Following up with further studies, the researchers found an explanation for their observations: the new lymphatic vessels created by the melanoma tumor secrete the chemokine CCL21, which actively attracts naïve (undifferentiated) T cells into the tumor's immunosuppressed microenvironment. (
  • A novel two-step process called adoptive transfer resulted in more than 50% tumor shrinkage in 6 of 13 patients with malignant melanoma, said Dr. (
  • Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells. (
  • Notch activation in thymic epithelial cells induces development of thymic microenvironments. (
  • 5 , 13 Activated macrophages can also induce epithelial-mesenchymal transition (EMT) forming fibroblasts by secreting matrix metalloproteinase 9. (
  • Differential epithelial growth in tissue-engineered larynx and trachea generated from postnatal and fetal progenitor cells Biochem Biophys Res Commun. (
  • Compared with conventional T cells, these innate T cells, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and H2-M3-specific T cells, are selected by interaction with hematopoietic cells rather than thymic epithelial cells, and their development is dependent on IL-15 and the SAP (SLAM-associated protein) signaling pathway [ 1 ]. (
  • Squamous cell carcinoma (SCC) can occur on a number of epithelial surface tissues ranging from the skin and lung to the esophagus and oropharynx, and collectively, are the most common form of cancer in the world. (
  • FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFκB signaling pathway. (
  • The Role of Myeloid-Derived Suppressor Cells in Viral Infection. (
  • The production of reactive nitrogen species by myeloid-derived suppressor cells (MDSCs) within the TME leads to T cell exclusion. (
  • Recently, it was shown that CCL3, CCL4, and CCL5 secreted by tumor-infiltrating myeloid-derived suppressor cells recruit high numbers of Tregs favoring lymphoma growth ( 9 ). (
  • Importantly, we also show recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented HPV16E7 epitope by A9 TCR transgenic CD4+ T cells. (
  • This requirement is well illustrated by the classic double transgenic mouse experiment in which coexistence of overexpression of a target antigen (a viral protein) in the ß cells of the islets of Langerhans and overexpression of T cells specific for this antigen does not lead to diabetes without activation of the said T cells by infection with the specific virus. (
  • Genetic labeling with bioluminescence imaging (BLI) and positron emitting tomography (PET) reporter genes allowed visualization of the distribution and antigen-specific tumor homing of TCR transgenic T cells, with trafficking correlated with antitumor efficacy. (
  • Accumulating evidence has revealed that manipulation of bone marrow-derived mesenchymal stem cells (BM-MSCs) may have the potential to control or even prevent RA, but BM-MSC-based therapy faces many challenges, such as limited cell availability and reduced clinical feasibility. (
  • Several potentially pathogenic islet/β cell autoantigens have been identified by their reactivity with circulating antibodies or T cells in rodents and humans with subclinical or clinical IDDM, particularly insulin, glutamic acid decarboxylase (GAD), and a tyrosine phosphatase, IA-2 ( 9 ). (
  • Clinical relevance for these data was suggested by the observation that myeloid cells were the predominant source of PNT in human lung, pancreatic, and breast cancer samples. (
  • The very poor survival of donor cells is one of the challenges that need to be overcome before CSC-based therapies become a clinical reality. (
  • Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. (
  • These results confirm the efficacy of autologous T-cell transfer therapy in a solid tumor and provide in-depth characterization of persistent T cells in a clinical context. (
  • Thus, any clinical application of the target cells is exclusively within the responsibility of the user of a CliniMACS System. (
  • To evaluate the safety and feasibility for adoptive transfer of T cells gene-modified to express such CARs, we initiated a pilot clinical trial using autologous T cells expressing an anti-CD19 CAR including both CD3-ζ and the 4-1BB costimulatory domain (CART19 cells) to target CD19 + malignancies. (
  • Immunosuppression - Decreased T cell infiltration and worse clinical outcome have been correlated with elevated VEGF levels along with expression of either B7-H3 or EDNRB/ET B R on tumor vessels. (
  • Various clinical studies show that CAR-T cells are able to induce complete remission of diffuse large B cell lymphoma and acute lymphoblastic leukemia . (
  • T cells which target both CD19 and CD22 are also being studied in some early phase clinical studies. (
  • Results from previous clinical trials demonstrate that with the use of CAR-T cells in hematological malignancies, treated patients who were refractory to other forms of treatment effectively achieved a complete response (CR). (
  • Among various types of stem cells being investigated, c-kit + cardiac stem cells (CSCs) appeared to be particularly promising because they are capable of differentiating into cardiomyocytes, smooth muscle cells, and endothelial cells [ 5 ]. (
  • The accumulation of oxLDL in the vessel wall stimulates the overlying endothelial cells to produce a number of proinflammatory molecules, including adhesion molecules such as the intercellular adhesion molecule-1, the vascular cell adhesion molecule-1, and endothelial selectin (E-selectin), as well as growth factors such as macrophage colony-stimulating factor. (
  • ligation of CD40 on endothelial cells induces VCAM-1 expression (107). (
  • Basic fibroblast growth factor (bFGF or FGF2), a potent mitogen for many cell types, including airway smooth muscle cells, fibroblasts, and endothelial cells (Redington et al. (
  • PD-L1 is constitutively expressed on mouse APCs (DCs, macrophages, and B cells) and T cells and is further up-regulated upon activation. (
  • Giavridis T, Van Der Stegen SJC, Eyquem J, Hamieh M, Piersigilli A, Sadelain M. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade letter. (
  • Another powerful approach to clarify the role of macrophages in renal disease has been the use of adoptive transfer techniques. (
  • 20 Transfer of macrophages activated by lipopolysaccharide, but not resting macrophages, also exacerbate renal injury in adriamycin nephrosis. (
  • 21 In the latter studies, transferred macrophages accumulate progressively in sites of injury and as few as 10,000 macrophages per mouse are sufficient to exacerbate disease. (
  • Can Alveolar Macrophages Made from Stem Cells Achieve Functional Rescue of Lung Diseases? (
  • The cellular infiltrates of active sclerotic lesions include CD4+ T cells (Th1 with some Th0 and Th2), CD8+ T cells, and macrophages (microglia and monocytes) (1-8). (
  • The production of interleukin (IL)-12 by macrophages clearly plays an important role in the maturation of Th1 cells (10). (
  • The cellular infiltrates of active sclerotic lesions are dominated by cells of the monocytic lineage (macrophages and microglial cells) (6-8). (
  • Infiltrated macrophages are found within renal diabetic tissues, and recent studies demonstrated that macrophage-derived products can induce further inflammation in the diabetic kidney ( 33 - 36 ). (
  • 1989) Removal of neuroblastoma cells from bone marrow by a direct monoclonal antibody rosetting technique. (
  • TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. (
  • Using gene transfer technologies, T cells can be genetically modified to stably express antibody binding domains on their surface that confer novel antigen specificities that are major histocompatibility complex (MHC)-independent. (
  • Normal B cells also express CD19 on their surfaces, which help to activate the antibody response so that pathogens are killed. (
  • Our study will be of interest to a broad range of basic researchers in cell biology, immunology, rheumatology as well as clinicians. (
  • 1 Department of Immunology and 2 Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. (
  • In addition, influenza virus-immune Tc cells are directed predominantly against the internal viral proteins, which are commonly shared among influenza A viruses ( 19 , 20 , 51 , 54 , 58 , 59 ). (
  • Further, being non-MHC dependent means that the T cells are not thwarted by mutations affecting antigen processing (TAP proteins) or down-regulation of MHC that can lead to tumor evasion ( 3 , 4 ). (
  • Reactive nitrogen species can induce the nitration of proteins. (
  • The T cells are further labelled with fluorescent proteins by retroviral gene transfer to perform intravital imaging by two-photon microscopy. (
  • In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. (
  • Gene expression profiling studies have shown that intratumoral expression of chemokines, indeed, correlate with T-cell infiltration ( 13 ). (
  • Clonal anergy in CD4+ T cells is established as a result of the activation of a program of gene expression that is dependent on the transcription factor NFAT. (
  • 2000) Phase I study of chemokine and cytokine gene-modified autologous neuroblastoma cells treatment of relapsed/refractory neuroblastoma using an adenoviral vector. (
  • Adoptive transfer of gene-modified T cells induces cancer regression in heavily pretreated patients. (
  • An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer. (
  • Retinoic acid treatment also decreased c-myb gene expression in human leukemia cells. (
  • and suppress via a mechanism that requires cell-to-cell contact ( 3 ). (
  • Although Tr1 cells must encounter their antigen to exert these effects, once the Tr1 cells are activated, they suppress in a non-antigen-specific manner. (
  • Fig. 2 B reg cells suppress IL-13 + ILC2s in an IL-10-dependent manner. (
  • Adoptive transfer of mature T cells, thymus grafts, or more elegant experimental systems in which MHC molecules were transiently expressed in the thymus have been used to study this issue. (
  • Most information concerning the effect of vaccines on the pancreatic β cells derives from animal studies. (
  • However, till this point it is unclear whether these vaccines are protective against HPV induced malignancies other than cervical cancer. (
  • In November 2007, a large multinational trial called Step, evaluating the lead candidate in what the HIV vaccine field termed T cell-based vaccines, was halted at its first interim analyses because of the vaccine's lack of efficacy [1,2] . (
  • Another concept concerning naive T cells has also been challenged by new findings. (
  • OBJECTIVE: In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4(+) cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge. (
  • Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. (
  • Conventional T cells take on naive phenotypes when they emigrate out from the thymus, whereas innate T cells from the thymus are phenotypically of the effector/memory form [ 1 ]. (
  • Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. (
  • Tr1 cells display a unique cytokine production profile that is distinct from that of T helper (Th)-0, Th1, or Th2 cells. (
  • It is further demonstrated that an initial low presence of cytokine message and protein is disappearing rather fast, whereas the triggering of endogenous TCR/CD3 in the same cells leads to normal prolonged cytokine production. (
  • Alternative strategies, such as stem cell-based therapies, are urgently needed [ 2 ]. (
  • Stem cell-based therapies are promising in repairing cardiac damage due to ischemia-reperfusion (I/R) injury [ 3 , 4 ]. (
  • Non-small cell lung cancers are frequently driven by specific genetic alterations that can be targeted by precision medicine therapies. (
  • Recently, two CAR-T cell therapies gained approval from the United States Food and Drug Administration (USFDA) for these two hematological cancers. (
  • These cells are also effective in patients with blood cancers which have relapsed or are refractory to existing therapies. (
  • To improve the efficacy of these T cell therapies, several strategies are being investigated. (
  • One implication is that future immune-based therapies for cancers and other diseases might get effective results from adoptive transfer of small numbers of individual T cells. (
  • Optimal binding strength is believed to be the most important predictor of success in adoptive transfer therapies. (
  • These cells play a central role in the immune response to viral infection and tumor surveillance. (
  • In addition, selected chemotherapies may promote immunogenic cell death, which stimulates the antitumor immune response ( 14 ). (
  • CTLA-4 plays a major role in suppressing the T-cell immune response. (
  • In this study, we demonstrated that antigen-specific CD8(+) T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1-based DNA vaccine. (
  • On the other hand, the innate immune response, which includes phagocytic cells, antimicrobial peptides, and the complement system, has been viewed to be primarily involved in the initial defense against infection. (
  • Little is known however on the mechanisms that regulate tumor-induced hyporesponsiveness in T helper cells. (
  • Polarization of AQP4-reactive T cells to the T-helper-17 led to CNS inflammation characterized by demyelination and T cell infiltration into the spinal cord, optic nerve, and brain. (
  • Our data indicate that TCR transfer is feasible as an alternative strategy to generate human HPV16 specific CD4+ T helper cells for the treatment of patients suffering from cervical cancer and other HPV16 induced malignancies. (
  • The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)-a potentially life‐threatening complication. (
  • The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T-cell infiltration during Ang II-induced hypertension is sex dependent. (
  • This review focuses on the molecular mechanisms of leukocyte recruitment into the diabetic kidney and the involvement of immigrated immune cells in the damage to renal tissues. (
  • DN is associated with the expansion of mesangial cells and development of characteristic features of renal injury, such as thickening of the glomerular basement membrane. (
  • The facts that glaucoma patients exhibit increased titers of antibodies against Helicobacter pylori and that immunization with HSPs in rats induces glaucomatous neural damage are in line with this possibility 11 . (
  • These data support a direct role of HCV in the pathogenesis of this lymphoproliferative disorder, together with the fact that 60%-80% of patients with MCII are infected with HCV and that effective anti-HCV treatment induces significant remissions of MCII [ 4 ]. (
  • All patients received a single cycle of fludarabine and cyclophosphamide, not intended as a direct cytotoxic therapy, but rather as a lymphocyte-depleting regimen before cell transfer to enhance T-cell engraftment and efficacy. (
  • The 4 panels correspond to tissue from 4 diffuse large B cell lymphoma patients. (
  • Loss of CD37 on neoplastic cells in patients with diffuse large B cell lymphoma (DLBCL) directly correlated with activation of the IL-6 signaling pathway and with worse progression-free and overall survival. (
  • Adoptively transferred NY-ESO-1 c259 cells showed antitumor activity in patients with synovial sarcoma. (
  • D'Angelo and colleagues sought to identify biological correlates and further evaluate the safety and feasibility of NY-ESO-1 + autologous T-cell therapy in the initial cohort of a pilot trial of patients with synovial sarcoma. (
  • TCRBV sequencing of the apheresis CD8 + T cells and NY-ESO1 + CD8 + T cells in responding patients further showed that persistent clones were derived from a preexisting pool of NY-ESO1-experienced stem cell/central T cells. (
  • However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. (
  • Therefore, other methods to treat patients suffering from cervical cancer and HPV induced malignancies should be explored. (
  • Adoptive transfer of HPV specific T cells could be an attractive strategy to treat patients suffering from HPV induced malignancies. (
  • Some of the findings from one of these patients are described in ( 9 ), which reports that this treatment results in tumor regression, CART19 cell persistence, and the unexpected occurrence of delayed tumor lysis syndrome. (
  • Acute cerebral ischaemia induces severe immunosuppression, 2-6 resulting in enhanced susceptibility to respiratory and urinary tract infections, which are the leading cause of death in stroke patients. (
  • Indeed, HBZ is expressed in infected cells isolated from asymptomatic carriers but, more importantly, in malignant cells from ATL patients. (
  • In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. (
  • In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8 + T cells. (
  • Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells. (
  • Treated tEAU rats had fewer R16-specific Th1 and Th17 cells, but increased numbers of Tregs. (
  • Innate immune cells are a first-line defense against pathogens and are thought to respond consistently to infection, regardless of previous exposure, i.e., they do not exhibit memory of prior activation. (
  • Thus, these experiments identify an ability of innate immune cells to retain an intrinsic memory of prior activation, a function until now attributed only to antigen-specific adaptive immune cells. (
  • In concert with other members of the innate response, NK cells are important for the initial control of many viral and bacterial pathogens ( 5 ⇓ - 7 ). (
  • Natural killer cells represent an important cellular component of the innate immune system. (
  • T-cell immunoglobulin and mucin domain 4 (TIM-4) signaling in innate immune-mediated liver ischemia-reperfusion injury. (
  • Here, we show that IL-4-induced innate CD8+ T cells are able to effectively control chronic virus infection. (
  • Previous data suggest that innate T cells might serve as a first-line of defense against certain bacterial pathogens. (
  • IL-4-induced innate CD8+ T cells are a unique subset of innate T cells that were recently identified in both mouse and human. (
  • Thereby, IL-4-induced innate CD8+ T cells provide an effective barrier to the establishment of persistent infection via effective virus control during the early phase of viral infection. (
  • Collectively our data show that IL-4-induced innate CD8+ T cells works as an early defense mechanism against chronic viral infection. (
  • Memory-like CD8 + T cells expressing eomesodermin (Eomes) are another subset of innate T cells [ 3 ]. (
  • however, this type of CD8 + T cells has unique characteristics that make them different from MHC class Ib-restricted innate T cells. (
  • The innate response relies on immediate recognition of antigenic structures common to many microbes by a selected set of immune cells with rapid effector function [Hoffman et al. (
  • Numerous groups have suggested that permanent interactions between T cells and self-peptide/self-MHC molecule complexes are required for T cell survival in the periphery ( 1 - 5 ). (
  • CP-EL-4 cells loaded with control peptide. (
  • G - I ) Experiments were performed essentially as described in A - C , except that EG-7 cells were used as targets instead of peptide-loaded EL-4 cells. (
  • DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. (
  • Recurrent EAU was induced in Lewis rats by interphotoreceptor retinoid-binding protein (IRBP) R16-peptide specific T cells (tEAU). (
  • In conclusion, these findings clearly demonstrate that iVα14 NKT cells are required to participate in allergen-induced Th2 airway inflammation through a CD1d-dependent mechanism. (
  • Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats. (
  • Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. (
  • Inflammation-induced tumor cell dedifferentiation resulted in loss of the tumor antigen and relapse. (
  • T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. (
  • In the context of MCMV infection, interaction of m157 (the MCMV-encoded ligand for Ly49H) with Ly49H results in activation of Ly49H-expressing NK cells. (
  • In this study, we examined the efficacy of synthetic long peptides (SLPs) as a CD4 + and CD8 + T cell-eliciting preventive vaccine approach against mouse CMV (MCMV) infection. (
  • While CD4 + T cells seem to be more crucial in the early phase after infection, CD8 + T cells are imperative during latency and harbor superior protective properties upon rechallenge ( 6 - 9 ). (
  • Injection of such laboratory-derived phase II variants into guinea pigs resulted in infection and reversion to phase I. However, plaque-purified (cloned) isolates of the Nine Mile Strain phase II organisms do not undergo phase reversion and are avirulent since inoculation of susceptible animals with phase II cells does not result in infection nor can viable phase II or phase I organisms be recovered from the spleens of these animals. (
  • T98G cells are highly permissive for lytic WNV-infection as demonstrated by the production of infectious virus titre and the development of a characteristic cytopathic effect. (
  • Therefore, thorough knowledge of the molecular mechanism of WNV-induced neural cell death will allow us to better understand the progression of WNV infection and the associated neurological pathology. (
  • Although the size and diversity of the lymphocyte repertoire make it likely that there is an antigen, a specific lymphocyte for any given pathogen, the frequency of these cells can be extremely low and normally will not be sufficient to protect the host against a primary infection. (
  • It is this process of clonal selection and the ultimate perpetuation of these antigen-specific memory cells that protects against a secondary infection. (