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.
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.
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.
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.
A classification of lymphocytes based on structurally or functionally different populations of cells.
The number of LYMPHOCYTES per unit volume of BLOOD.
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.
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.
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.
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.
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.
An encapsulated lymphatic organ through which venous blood filters.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
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.
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.
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.
A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
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.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
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 number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.
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.
Antibodies produced by a single clone of cells.
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.
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)
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 CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
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.
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.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
Sites on an antigen that interact with specific antibodies.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th 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.
Established cell cultures that have the potential to propagate indefinitely.
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
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.
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 integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.
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.
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 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.
Cell surface glycoproteins on lymphocytes and other leukocytes that mediate adhesion to specialized blood vessels called high endothelial venules. Several different classes of lymphocyte homing receptors have been identified, and they appear to target different surface molecules (addressins) on high endothelial venules in different tissues. The adhesion plays a crucial role in the trafficking of lymphocytes.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
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.
Glycoproteins found on the membrane or surface of cells.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
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.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
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 fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).
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).
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.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Substances that are recognized by the immune system and induce an immune reaction.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
The major group of transplantation antigens in the mouse.
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.
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.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
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.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
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.)
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)
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
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.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A class of lymphocytes characterized by the lack of surface markers specific for either T or B lymphocytes.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
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.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
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 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.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
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.
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Elements of limited time intervals, contributing to particular results or situations.
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 family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
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.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Substances elaborated by viruses that have antigenic activity.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
Adherence of cells to surfaces or to other cells.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
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).
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Reduction in the number of lymphocytes.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
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).
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.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
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.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
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.
Proteins prepared by recombinant DNA technology.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A protein extracted from boiled culture of tubercle bacilli (MYCOBACTERIUM TUBERCULOSIS). It is used in the tuberculin skin test (TUBERCULIN TEST) for the diagnosis of tuberculosis infection in asymptomatic persons.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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 largest lymphatic vessel that passes through the chest and drains into the SUBCLAVIAN VEIN.
Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
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.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
The rate dynamics in chemical or physical systems.
Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A general term for various neoplastic diseases of the lymphoid tissue.
An immunological attack mounted by a graft against the host because of tissue incompatibility when immunologically competent cells are transplanted to an immunologically incompetent host; the resulting clinical picture is that of GRAFT VS HOST DISEASE.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).
Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
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.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
An energy dependent process following the crosslinking of B CELL ANTIGEN RECEPTORS by multivalent ligands (bivalent anti-antibodies, LECTINS or ANTIGENS), on the B-cell surface. The crosslinked ligand-antigen receptor complexes collect in patches which flow to and aggregate at one pole of the cell to form a large mass - the cap. The caps may then be endocytosed or shed into the environment.
Surgical removal of the thymus gland. (Dorland, 28th ed)
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A classification of B-lymphocytes based on structurally or functionally different populations of cells.
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
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.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
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.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Unstable isotopes of chromium that decay or disintegrate emitting radiation. Cr atoms with atomic weights of 46-49, 51, 55, and 56 are radioactive chromium isotopes.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
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.
Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.

Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. (1/7255)

The transcription factor NF-ATc is synthesized in three prominent isoforms. These differ in the length of their C terminal peptides and mode of synthesis. Due to a switch from the use of a 3' polyA site to a more proximal polyA site, NF-ATc expression switches from the synthesis of the two longer isoforms in naive T cells to that of short isoform A in T effector cells. The relative low binding affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems to contribute to its neglect in naive T cells. These alternative polyadenylation events ensure the rapid accumulation of high concentrations of NF-ATc necessary to exceed critical threshold levels of NF-ATc for gene induction in effector T cells.  (+info)

Development of CD8+ effector T cells is differentially regulated by IL-18 and IL-12. (2/7255)

We investigated the effects of IL-18 on the development of CD8+ effector T cells in DBA/2 anti-BDF1 whole spleen cell MLC and compared the results with those of IL-12. Addition of IL-18 to the MLC resulted in a twofold increase in CD8/CD4 ratios compared with the control cultures when cells were expanded in IL-2-containing medium following MLC. Purified CD8+ T cells recovered from the IL-18-stimulated MLC produced 20- to 30-fold more IFN-gamma after secondary stimulation with C57BL/6 spleen cells or anti-CD3 mAb, and exhibited strong allospecific CTL activity. Neither IL-18 nor IL-18-supplemented culture supernatants from DBA/2 anti-BDF1 MLC induced type I CD8+ effector T cells when purified CD8+ T cells were used as responder cells in primary MLC. Furthermore, CD4+ T cell depletion from the responder cells abrogated the IL-18-induced increase in secondary IFN-gamma production by CD8+ T cells, suggesting that IL-18-induced type I effector CD8+ T cell development was CD4+ T cell dependent. In marked contrast, adding IL-12 to primary MLC decreased CD8/CD4 ratios by 50% and suppressed secondary IFN-gamma production and CTL activity by CD8+ T cells regardless of concentration, whereas Th1 development was promoted by IL-12. Moreover, both IL-12 and IL-18 efficiently induced type I CD8+ effector T cells in C57BL/6 anti-BDF1 MLC. These findings show that IL-18 plays an important role in the generation of type I CD8+ effector T cells, and further suggest that functional maturation of CD8+ T cells is differentially regulated by IL-18 and IL-12.  (+info)

Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. (3/7255)

The effects of inflammatory cytokines on naive T cells have been studied using MHC protein/peptide complexes on microspheres, thus avoiding the use of APCs whose functions may be affected by the cytokines. IL-1, but not IL-12, increased proliferation of CD4+ T cells in response to Ag and IL-2, which is consistent with effects on in vivo priming of CD4+ cells. In contrast, proliferation of CD8+ T cells to Ag and IL-2 required IL-12, and IL-12 replaced adjuvant in stimulating an in vivo response to peptide. These results support a model in which distinct inflammatory cytokines act directly on naive CD4+ and CD8+ T cells to provide a third signal, along with Ag and IL-2, to optimally activate differentiation and clonal expansion.  (+info)

Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. (4/7255)

This study shows that the normal thymus produces immunoregulatory CD25+4+8- thymocytes capable of controlling self-reactive T cells. Transfer of thymocyte suspensions depleted of CD25+4+8- thymocytes, which constitute approximately 5% of steroid-resistant mature CD4+8- thymocytes in normal naive mice, produces various autoimmune diseases in syngeneic athymic nude mice. These CD25+4+8- thymocytes are nonproliferative (anergic) to TCR stimulation in vitro, but potently suppress the proliferation of other CD4+8- or CD4-8+ thymocytes; breakage of their anergic state in vitro by high doses of IL-2 or anti-CD28 Ab simultaneously abrogates their suppressive activity; and transfer of such suppression-abrogated thymocyte suspensions produces autoimmune disease in nude mice. These immunoregulatory CD25+4+8- thymocytes/T cells are functionally distinct from activated CD25+4+ T cells derived from CD25-4+ thymocytes/T cells in that the latter scarcely exhibits suppressive activity in vitro, although both CD25+4+ populations express a similar profile of cell surface markers. Furthermore, the CD25+4+8- thymocytes appear to acquire their anergic and suppressive property through the thymic selection process, since TCR transgenic mice develop similar anergic/suppressive CD25+4+8- thymocytes and CD25+4+ T cells that predominantly express TCRs utilizing endogenous alpha-chains, but RAG-2-deficient TCR transgenic mice do not. These results taken together indicate that anergic/suppressive CD25+4+8- thymocytes and peripheral T cells in normal naive mice may constitute a common T cell lineage functionally and developmentally distinct from other T cells, and that production of this unique immunoregulatory T cell population can be another key function of the thymus in maintaining immunologic self-tolerance.  (+info)

Decreased IL-12 production underlies the decreased ability of male lymph node cells to induce experimental autoimmune encephalomyelitis. (5/7255)

Myelin basic protein (MBP)-specific T lymphocytes from male SJL mice were shown to be less encephalitogenic than MBP-specific T lymphocytes from females. Mechanisms underlying this gender difference in the induction phase of EAE were examined. Following immunization with MBP, draining lymph nodes contained fewer cells, and Ag-specific proliferative responses were decreased in males as compared with females. These gender differences in the proliferative response were not unique to MBP-specific responses since they were also observed after immunization with hen eggwhite lysozyme. Short-term MBP-specific T cell lines derived from females and males mapped with identical specificity, indicating no defect in the ability of male APCs to process Ag. Interestingly, IL-12 and IFN-gamma production was decreased following Ag-specific stimulation of draining lymph node cells (LNC) from males as compared with females, but IL-10 and IL-4 were no different. While male-derived LNCs were less encephalitogenic than female derived LNCs, cotransfer and coculture of male LNCs with female LNCs demonstrated that male LNCs were not immunosuppressive. Administration of IL-12 to LNCs from male mice enhanced encephalitogenicity. These data indicate that deficient endogenous IL-12 production within draining LNCs of male SJL mice is central to gender differences in the induction phase of experimental autoimmune encephalomyelitis.  (+info)

Emergence of regulatory CD4+ T cell response to repetitive stimulation with antigen-presenting cells in vitro: implications in designing antigen-presenting cell-based tumor vaccines. (6/7255)

Because APCs play a crucial role in the generation of T cell-mediated immune responses, numerous clinical trials with APC-based vaccines have been initiated in different types of human cancers. Encouraging results have emerged from some of these initial studies. Thus far, APC-based vaccinations usually include multiple rounds of immunization. With this approach, although we and others have detected induction of Ag-specific CTL responses in vaccinated patients after stimulation with the same APC-based immunogen, in vitro we also find that repetitive in vitro stimulation with Ag-loaded APC can, at times, lead to the emergence of noncytolytic CD4+ T cells exhibiting the characteristic phenotype of Th2 cells. These noncytolytic CD4+ T cells synthesize large quantities of type 2 cytokines such as IL-4 and IL-10 on stimulation with the autologous APC or tumor cells in an MHC class II-restricted manner. Further, these CD4+ T cells and a cell-free supernatant factor block the activation of fresh T lymphocytes. The supernatant factor also exhibits a marked inhibitory effect on the expression of the costimulatory molecules, CD80 and CD86, by APC. The inhibitory effect of the supernatant factor can be abrogated by neutralizing IL-10 in the supernatant. These observations therefore have implications in the APC-based tumor vaccine protocol design.  (+info)

Regulation of apoptosis in mature alphabeta+CD4-CD8- antigen-specific suppressor T cell clones. (7/7255)

The regulation of apoptosis in mature CD4+ or CD8+ alphabeta+ T cells has been well studied. How the survival and death is regulated in peripheral CD4-CD8- (double negative, DN) alphabeta+ T cells remains unknown. Recent studies suggest that peripheral DN T cells may play an important role in the regulation of the immune responses mediated by CD4+ or CD8+ T cells. Here, we used immunosuppressive DN T cell clones to elucidate the mechanisms involved in the regulation of death and survival of alphabeta+ DN T cells. The DN T cell clones were generated from the spleen cells of 2C transgenic mice, which express the transgenic TCR specific for Ld and permanently accepted Ld+ skin allografts after pretransplant infusion of Ld+ lymphocytes. We report that 1) the mature DN T cells are highly resistant to TCR cross-linking-induced apoptosis in the presence of exogenous IL-4; 2) Fas/Fas-ligand and TNF-alpha/TNFR pathways do not play an apparent role in regulating apoptosis in DN T cells; 3) the DN T cells constitutively express a high level of Bcl-xL, but not Bcl-2; 4) both Bcl-xL and Bcl-2 are up-regulated following TCR-cross-linking; and 5) IL-4 stimulation significantly up-regulates Bcl-xL and c-Jun expression and leads to mitogen-activated protein kinase phosphorylation in DN T cells, which may contribute to the resistance to apoptosis in these T cells. Taken together, these results provide us with an insight into how mature DN T cells resist activation-induced apoptosis to provide a long-term suppressor function in vivo.  (+info)

Regulation of the mucosal immune response. (8/7255)

Infectious diseases continue to exact an extensive toll on populations living closest to the equatorial regions of the globe. A substantial proportion of these infections gain access to the host via the mucosal tissues. Thus, the development of new vaccines that enhance mucosal immunity is considered to be of paramount importance in order to prevent or limit the impact of these infections. Mucosal immune responses must discriminate between commensal flora within the lumen and potential pathogens. These responses are highly adapted to induce protection without excessive amounts of inflammation. The balances that regulate mucosal immune and inflammatory responses have to be understood if effective mucosal immunity is to be induced through local immunization. This review will summarize some of the unique properties of mucosal immune responses and focus on recent advances that have significantly influenced our understanding of the regulation of immune and inflammatory responses following infection.  (+info)

TY - JOUR. T1 - In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines. AU - Hippen, K. L.. AU - OConnor, R. S.. AU - Lemire, A. M.. AU - Saha, A.. AU - Hanse, E. A.. AU - Tennis, N. C.. AU - Merkel, S. C.. AU - Kelekar, A.. AU - Riley, J. L.. AU - Levine, B. L.. AU - June, C. H.. AU - Turka, L. A.. AU - Kean, L. S.. AU - MacMillan, M. L.. AU - Miller, J. S.. AU - Wagner, J. E.. AU - Munn, D. H.. AU - Blazar, B. R.. PY - 2017/12. Y1 - 2017/12. N2 - Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently ...
The atheroprotective effect paralleled an induction of Treg suppression of apoB-100-specific effector T cells and an increase in IL-10+ CD4+ T cells. Therefore, our data suggest that nasal immunization with p210-CTB protects against atherosclerosis by inducing antigen-specific, IL-10+ regulatory Tr1 cells. It is unlikely that atheroprotection involved the immunosuppressive cytokine TGF-β because nasal immunization with p210-CTB also reduced atherosclerosis in mice lacking a functional TGF-β receptor on T cells.. Antigen-specific as well as antigen-independent effects have been reported in studies of Treg.25 Several studies of autoimmune diseases support the regulation model according to which Treg suppresses conventional effector T cells with the same antigen specificity. Other investigators report that Treg exerts major effects on antigen-presenting cells in an antigen-independent manner. Our data clearly show that antigen-specific atheroprotection was paralleled by inhibition of ...
CD4+Foxp3+ regulatory T cells (Treg)s are essential for the prevention of autoimmunity. Treg lineage commitment requires T cell receptor (TCR) interactions that induce expression of foxp3, whose protein product enforces Treg fate. Treg homeostasis is critical for self-tolerance and is achieved through both Treg generation and maintenance. Treg maintenance occurs in part through a process of self-renewing cell division of existing Tregs. This self-renewing Treg division has been shown to be TCR dependent. Despite the crucial role of the TCR in Treg generation and maintenance, neither the specific signaling pathways that control Treg generation nor the nature of the TCR signals required for their division in the periphery are well understood. Here, we demonstrated that dendritic cells (DC)s coordinate Treg division in vitro. DCs elicit interleukin-2 (IL-2) production from conventional CD4+ T cells (Tconv)s in a major histocompatibility complex class II (MHCII)-dependent fashion. Tconv-derived IL-2
The data presented here provide new insight into the biology of regulatory T cells within the context of a human autoimmune disease. CD4+CD25high T cells isolated from patients with active RA, although still anergic, show compromised function as demonstrated by their inability to regulate proinflammatory cytokines released by effector T cells and monocytes. After Infliximab treatment, regulatory T cell-mediated suppression was restored to the level found in healthy individuals, whereas only a partial restoration was seen in regulatory T cells isolated from patients responding to methotrexate. Although it is well documented that Infliximab blocks both soluble and transmembrane TNFα, resulting in a strong inhibition of other proinflammatory cytokines, there is no unanimity about the effects of methotrexate on cytokine production in RA (21, 22). If proinflammatory cytokines are not efficiently suppressed in methotrexate-treated patients, this could have a deleterious effect on the function of ...
Description of disease T-suppressor cell. Treatment T-suppressor cell. Symptoms and causes T-suppressor cell Prophylaxis T-suppressor cell
Human regulatory T cells (Treg) have been variously defined as CD4(+)CD25(+), CD4(+)CD25(high) or CD4(+)CD25(high)FOXP3(+) cells which are responsible for maintaining peripheral tolerance. Their isolation from human peripheral blood or tissues depends on the expression level of CD25(IL-2Ralpha) - a surface marker which is also expressed on activated effector helper T cells. CD39, a cell surface associated ectonucleotidase, can be used to purify Treg with strong suppressor functions. The CD4(+)CD39(+) T cells catalyze cleavage of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is then further cleaved to adenosine. CD4(+)CD39(+) T cells largely overlap with CD4(+)CD25(high)FOXP3(+) but not CD4(+)CD25(+) T cell subset, and mediate equally potent immune suppression. Thus, CD39 surface marker can be successfully used for routine isolation of functionally-active human Treg from the peripheral blood of healthy donors or patients with cancer for studies of their role in health and disease.
Paterson AM, Lovitch SB, Sage PT, Juneja VR, Lee Y, Trombley JD, Arancibia-Cárcamo CV, Sobel RA, Rudensky AY, Kuchroo VK, et al. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med. 2015.
Regulatory T cells curb unwanted immune responses and regulate responses to microflora and it is now clear that regulatory T cells play an important role in a number of chronic inflammatory diseases of the gut. First, regulatory T cells are crucial in controlling immune responses to gastric autoantigens and thus preventing autoimmune gastritis and pernicious anemia. Second, regulatory T cells may modulate the response to Helicobacter pylori, thus affecting the ability of the immune system to clear the pathogen and mediate damage to the gastric mucosa. Finally, regulatory T cells play an important role in preventing damaging inflammatory responses to commensal organisms in the lower gut, thus guarding against inflammatory bowel diseases. In the present review, we examine the actions of regulatory T cells in the gut and conclude that further understanding of regulatory T cell biology may lead to new therapeutic approaches to chronic gastrointestinal disease ...
The mechanism of LN-specific, Ag-specific Treg enrichment might depend on factors regulating T cell homing to LN, encounter with self-Ag, and their retention in the LN. Homing of naive T cells and Treg to normal LN are known to involve CD62L, CCR7, and the chemokines CCL19 and CCL21 (15). Autoimmune diseases occur in mice deficient in CD62L or CCR7 (16, 17), for which we can now add a potential explanation: the loss of DS-Treg enrichment in regional LN. Treg retention may result from up-regulation of CD69 on Ag-specific Treg that temporarily sequester sphingosine 1-phosphate receptor type 1, which is required for T cell egress from LN (18). Additional mechanisms may involve Treg response to antiapoptotic and/or cellular proliferation signals (19). Constrained by T cell homeostatic mechanisms (20), the number or activity of DS-Treg in the regional LN would be maintained at a threshold 15- to 50-fold greater than those in the nondraining LN.. Additional mechanisms participate in Ag-specific Treg ...
Spellman, C W. and Daynes, R A., Properties of ultraviolet light-induced suppressor lymphocytes within a syngeneic tumor system. (1978). Subject Strain Bibliography 1978. 1859 ...
TY - JOUR. T1 - Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice. AU - Dwyer, Connor J.. AU - Bayer, Allison L. AU - Fotino, Carmen. AU - Yu, Liping. AU - Cabello-Kindelan, Cecilia. AU - Ward, Natasha C.. AU - Toomer, Kevin H.. AU - Chen, Zhibin. AU - Malek, Thomas. PY - 2017/12/19. Y1 - 2017/12/19. N2 - The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (Tregs). The contribution of polymorphisms in the gene encoding the IL-2 receptor subunit (IL2RA), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small. We investigated the mechanisms whereby a modest reduction in IL-2R signaling selectively in T lymphocytes influenced the development of diabetes in the NOD mouse model. The sensitivity of IL-2R signaling was reduced by about two- to threefold in Tregs from ...
We used a defined IL-2/αIL-2 complex that directs IL-2 to stimulate only intermediate-affinity IL-2 receptor (CD122/132) to promote tumor rejection and avoid regulatory T cell (Treg) expansion. However, it is unknown if IL-2/αIL-2 alters Treg function, as Tregs also express CD122/132. After challenge with ID8agg ovarian cancer (OC) cells, IL-2/αIL-2 greatly reduced tumor burden, and increased IFN-γ, TNF-α, CD44, and CD25 in CD4+ non-Tregs and CD8+ T cells, as expected. IL-2/αIL-2 was clinically effective, yet it lowered the ascites CD8+/FoxP3+ Treg ratio and increased per cell FoxP3 levels in Tregs, suggesting a change in Treg function. IL-2/αIL-2 decreased the ratio of CD62L+ central Tregs to CD44+ effector Tregs in ID8agg ascites, indicating modulation of Treg differentiation. Surprisingly, ascites Tregs produced IFN-γ, IL-2, and TNF-α in control-treated OC mice, which was abolished by IL-2/αIL-2, suggesting further alteration of Treg differentiation and function. CD25 (high-affinity ...
A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable
Kakita, N., Kanto, T., Itose, I., Kuroda, S., Inoue, M., Matsubara, T., Higashitani, K., Miyazaki, M., Sakakibara, M., Hiramatsu, N., Takehara, T., Kasahara, A. and Hayashi, N. (2012), Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: A crucial role of CD25−FOXP3− T cells. Int. J. Cancer, 131: 2573-2583. doi: 10.1002/ijc.27535 ...
The TF Foxp3 is a hallmark of Treg cells; however, Foxp3 is not sufficient to control the Treg program alone, and other TFs are important in this regard. This study demonstrates the fundamental role of Bcl11b in regulating the Treg signature program while repressing the innate lineage programs in mouse Treg cells. In the absence of Bcl11b, Treg cells were unable to exert their suppression function, which led to the inability to control multiorgan inflammation. Even when isolated from Bcl11b/Treg KO mosaic female mice, in the absence of inflammation, Bcl11b KO Treg cells failed to control CD45Rbhi CD4+ T cell-induced colitis in Rag1−/− mice. This failure was likely due to reduced levels of critical Treg suppression genes, including Il2ra, Ctla4, Nt5e, and Gitr. Mechanistic studies using genome-wide binding analysis of Bcl11b show that Bcl11b directly regulates the expression of many of these genes by binding to genomic regulatory regions, both in mouse and human Treg cells, thus making Bcl11b ...
CD4+ Foxp3+ regulatory T (Treg) cells belong to a distinct T cell lineage which develops in the thymus and is essential for the prevention of self-reactivity by suppressing peripheral auto-reactive T cells that escape thymic negative selection. IL-2/IL-2R signaling is crucial and non-redundant for the development of thymic Treg cells, as well as the homeostasis and competitive fitness of peripheral Treg cells. The central role of IL-2 in Treg biology is exemplified by the uncontrolled massive lymphoproliferation associated with IL-2-/-, IL-2Rα-/- and IL-2Rβ-/- mice which typically die by 4-12 week of age. It is noteworthy that a restored normal percentage and number of peripheral Treg cells in Bim-/- IL-2-/- mice did not rescue these mice from severe autoimmunity. Instead, additional IL-2 was still required for the proper functioning of peripheral Bim-/- IL-2-/- Treg cells. Consistently, in the current studies, we found that the development of thymic Treg cells was blocked with mostly CD4+ CD25-
SJL mice exhibit a unique gender-dependent bias in their immune response. Males mount an anti-inflammatory Th2 response, whereas females react with an inflammatory Th1 response, which correlates with susceptibility to experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis. Castration as well as macrophage transfer from females reverses the male phenotype. Utilizing this mouse strain for the study of gender-dependent mechanisms of immune regulation, the role of CD25 regulatory T cells was examined. These cells maintain a Th2 environment in naïve males by regulating macrophage responsiveness. Transfer of macrophages from naïve CD25+-depleted males into untreated males results in a Th1 response after immunization demonstrating that regulatory T cells directly influence macrophage function. Males have a two-fold increase in the number of regulatory T cells compared to females, but no difference in cell surface marker expression or in vitro suppressive action was detected. ...
While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by
FOXP3+CD4+ regulatory T cells (Tregs) are critical for immune homeostasis and respond to local tissue cues, which control their stability and function. We explored here whether developmental endothelial locus-1 (DEL-1), which, like Tregs, increases during resolution of inflammation, promotes Treg responses. DEL-1 enhanced Treg numbers and function at barrier sites (oral and lung mucosa). The underlying mechanism was dissected using mice lacking DEL-1 or expressing a point mutant thereof, or mice with T cell-specific deletion of the transcription factor RUNX1, identified by RNA sequencing analysis of the DEL-1-induced Treg transcriptome. Specifically, through interaction with αvβ3 integrin, DEL-1 promoted induction of RUNX1-dependent FOXP3 expression and conferred stability of FOXP3 expression upon Treg restimulation in the absence of exogenous TGF-β1. Consistently, DEL-1 enhanced the demethylation of the Treg-specific demethylated region (TSDR) in the mouse Foxp3 gene and the suppressive ...
Naive CD4(+) cells differentiate into T helper (Th1, Th2, Th9, Th17) and regulatory T (Treg) cells to execute their immunologic function. Whereas TGF-β suppresses Th1 and Th2 cell differentiation, this cytokine promotes Th9, Th17 and Foxp3(+) regulatory T cells depending upon the presence of other cytokines. IL-6 promotes Th17, but suppresses regulatory T cell differentiation. Moreover, natural but not TGF-β-induced regulatory T cells convert into Th17 cells in the inflammatory milieu. Here an update of T cell differentiation and conversion, as well as underlying mechanisms are given.. ...
University of California, San Francisco, San Francisco, CA. Manipulating human regulatory T cells (Tregs) offers the opportunity to induce tolerance in a clinical setting. However, low numbers of antigen-specific Tregs and Treg instability upon prolonged expansion have hampered the implementation of Treg-based therapies. Chimeric antigen receptor (CAR) technology has greatly expedited the generation of tumor antigen- specific effector T (Teff) cells. CARs are synthetic receptors comprising an extracellular antigen-binding domain and an intracellular signaling domain. The latter is commonly a fusion of CD28 and CD3z, allowing for potent T cell activation directly downstream of antigen recognition. Adoption of the CAR platform for Treg engineering represents a promising strategy to generate custom-made antigen-specific Tregs for therapy. Yet, there are marked differences in function and signaling between Tregs and Teff cells. Here, we interrogated CAR-mediated signaling in human Tregs and Teff ...
To what extent proinflammatory Th17 cells and defects in Treg-mediated regulation contribute to the development of type 1 diabetes in humans is highly debated. Here we show that the PLNs of patients with type 1 diabetes, unlike their PB, have an altered immune status due to the expansion of Th17 cells and the presence of CD25bright T cells epigenetically imprinted to have a regulatory activity but which lack a proper function.. Increased Th17 cells in the PB of children with diabetes has been recently reported (8), and Tan and colleagues (9) have demonstrated that these circulating IL-17-producing T cells may reside mainly within the CD4+CD45RA−CD25intFOXP3low cells. Although expressing FOXP3, this latter cell subset does not have suppressive activity, but rather, it has a helper function and contains proinflammatory cytokine-producing cells (40,41). Our data demonstrate that the expansion of Th17 immunity is also present in the target organ of patients with long-term diabetes. However, this ...
Peripheral immune tolerance requires a finely controlled balance between tolerance to self-antigens and protective immunity against enteric and invading pathogens. Self-reactive T cells sometimes escape thymic clonal deletion, and can subsequently provoke autoimmune diseases such as type 1 diabetes (T1D) unless they are controlled by a network of tolerance mechanisms in the periphery, including CD4+ regulatory T cells (Treg) cells. CD4+ Treg cells are characterized by the constitutive expression of the IL-2Rα chain (CD25) and preferentially express the forkhead winged helix transcriptional regulator Foxp3. These cells have been shown to possess immunosuppressive properties towards various immune cell subsets and their defects are thought to contribute to many autoimmune disorders. Strong evidence shows that IL-2 is one of the important stimulatory signals for the development, function and fitness of Treg cells. The non-obese diabetic (NOD) mouse model, a prototypic model of spontaneous autoimmunity,
CD4(+)CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4(+)CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4(+)CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4(+)CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4(+)CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4(+)CD25high T cells were ...
The upkeep of immune homeostasis requires regulatory T cells (Tregs). for a core property of regulatory T-cells. Regulatory T cells TPCA-1 (CD4 and CD8 Treg) dampen excessive immune responses and prevent or better autoimmune tissue damage while immune suppression exerted by Treg can impede anti-tumor immune responses. In contrast to effector T cells which rely on robust activation and differentiative plasticity Treg depend on preservation of a stable anergic and suppressive phenotype to maintain immune homeostasis (1 2 Although FoxP3+ CD4 Treg are remarkably stable (1 2 the genetic mechanisms that ensure phenotypic stability after expansion during inflammation infection Bombesin or autoimmunity i. e. conditions that most require maintenance of an inhibitory and anergic Treg phenotype are poorly comprehended. The Helios (Ikzf2) transcription factor (TF) is expressed by two regulatory T cell lineages- FoxP3+CD4+ and Ly49+CD8+ Treg (Fig. S1) TPCA-1 (3-6). To determine the contribution of Helios to ...
Inhibitory receptors on T cells, including lymphocyte activation gene 3 (LAG3), serve as brakes that limit immune-mediated damage to the host. LAG3 is expressed by exhausted conventional T cells in the tumor microenvironment and has emerged as a key target for tumor immunotherapy. The role of LAG3 in regulatory T cells (Tregs) has remained unclear. Using a mouse model of autoimmune diabetes, Zhang et al. report that Treg-specific deletion of LAG3 led to enhanced Treg proliferation and reduced the incidence of type 1 diabetes. Their studies highlight the cell-type dependence and context specificity of the role of LAG3 and call for a more holistic assessment of the functions of inhibitory receptors that emerge as targets for tumor immunotherapies. ...
FOXP3 is the master transcription factor of CD4+CD25+FOXP3+ T-regulatory (Treg) cells, and demethylation of the Treg-specific demethylation region (TSDR) of FOXP3 is considered a specific marker of stable, functionally competent thymic Tregs, allowing their discrimination from activated CD4+CD25+FOXP3+ T-effector cells. Assessment of TSDR demethylation in PBMC has thereby come to be regarded as a gold standard for calculating numbers of true Tregs. However, data regarding use of FOXP3 TSDR demethylation in PBMC were derived from healthy donor cells, i.e. mostly resting cells isolated from non-inflammatory conditions. Methods: We assessed FOXP3 TSDR demethylation in Tregs isolated from liver and kidney allograft recipients, as well as evaluating their number and phenotype (CD4, CD25, CD127, CTLA4, FOXP3), and assessed any correlations with the numbers of true Tregs calculated using FOXP3 TSDR demethylation in PBMC from the same samples. Results: Pediatric recipients had stable liver (n=53, 26 M) ...
The immunosuppressive effects of CD4⁺CD25⁺ regulatory T cells (Tregs) interfere with anti-tumor immune responses in cancer patients. In the first part of this work, we present a novel class of engineered Interleukin-2 (IL-2) analogues that antagonize the IL-2 receptor, for inhibiting Treg suppression. These antagonists are engineered for high affinity to the IL-2 receptor a subunit and low affinity to either the [beta] or [gamma] subunit, resulting in a signaling-deficient IL-2 analogue that sequesters the IL-2 receptor a subunit from wild type IL-2. Using this design, human and mouse IL-2 antagonists were generated with inhibition constants ranging from 200 pM to 5 nM in vitro. Genetic fusions with IgG2a Fc enhanced serum half-life up to 30 hours. In order to study the effects of IL-2 antagonism, Fc fragments with disrupted effector functions were used. Fc-antagonist fusions bound to but could not deplete peripheral Tregs. They downregulated CD25 on Tregs, but could not perturb Treg ...
Regulation of the immune response is important to avoid chronic inflammation and autoimmunity. Anergic/suppressive CD4+CD25+ T cells have been shown to be major contributors to this regulation. We have previously shown that the suppressive CD4+CD25+ T cells can suppress mitogenic and antigen-specific CD4+ T-cell responses in humans (EJI 2001, 31:1122; Immunology 2001, 104:6). In rheumatoid arthritis (RA), besides CD4+ T cells also monocytes play an important role in the disease process. Therefore we investigated whether the suppressive CD4+CD25+ T cells could affect monocyte activation as well as T-cell activation. CD4+ T cells and monocytes were isolated from peripheral blood mononuclear cells from healthy donors via MACS isolation techniques. CD4+ T cells were separated into CD4+CD25+ and CD4+CD25- T cells. T cells and monocytes were cocultured for two days without or with anti-CD3 mAb, after which proliferation, cytokine production and phenotypic markers were investigated. Coculture of ...
Definition of suppressor T cell in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is suppressor T cell? Meaning of suppressor T cell as a finance term. What does suppressor T cell mean in finance?
It has been reported that a growing and heterogeneous group of regulatory cell modulate immune response. In particular, regulation of CD8+ T lymphocyte effector functions is critical for tissue homeostasis and immune tolerance control. Here, we report that the co-expression of CD3 and CD56 molecules identify a novel human regulatory T cell population exerting suppressive activity on proliferation, cytotoxicity and IFN- production of TCR-activated human CD8+ T lymphocytes. Regulatory functions of human circulating CD3+CD56+ T lymphocytes require cell-to-cell contact and are exerted in both autologous and allogeneic conditions. Of note, CD3+CD56+ T cells are reduced and functionally impaired in children affected by Type 1 Diabetes (T1D), at disease onset. Conversely the frequency of this cell subset is increased in patients with prostate cancer. Taken together, our findings reveal that freshly isolated human CD3+CD56+ cells specifically control activation of human CD8+ T lymphocytes. ...
Differential Effects of IL-12 on Tregs and Non-Treg T Cells: Roles of IFN-γ, IL-2 and IL-2R. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation and solid organ transplantation. Current clinical approaches aim to boost Tregs in vivo either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized and targeted Treg product. Efforts to overcome these limitations and improve Treg-directed therapies are now under intense investigation in animal models and pre-clinical studies. Here we review cell and protein engineering-based approaches that aim to target different aspects of Treg biology including modulation of IL-2 signaling or FOXP3 expression, and targeted antigen-specificity using transgenic T cell
The data presented in this study show that Ets-1 is required for normal development and function of T reg cells and that defects in this cell subset were responsible for some of the immunological disorders in Ets-1−/− mice. Viable young mutant animals had reduced numbers of T reg cells in the spleen, but the frequency in the thymus appeared normal. In both sites, Ets-1−/− T reg cells had an unusual phenotype in that they expressed CD103 (Fig. 4 B), a marker typical of cells that experienced antigen under certain inflammatory conditions (Huehn et al., 2004; Suffia et al., 2005). This raised the possibility that the majority of thymic Ets-1−/− T reg cells were antigen-experienced recirculating cells, thereby masking an important quantitative deficit in thymic development of these cells. This was indeed the case, as supported by the very low frequency of thymic T reg cells in FTOCs (Fig. 4 C), in 5-d-old newborns (not depicted), and in mixed WT/KO chimeras analyzed at relative early ...
Regulatory T cells (Tregs) act by suppressing the activation and effector functions of innate and adaptive immune responses. we show that equivalent conclusions were drawn from the mix of markers utilized to define Tregs no matter. Our outcomes also showed elevated appearance of cell routine markers (Ki67 and cyclin B) in Tregs from neglected infected individuals, that have been reduced by HAART. However, the Treg phenotype in untreated patients was not consistent with a higher level of generalized activation, as they expressed very low levels of CD69, slightly elevated levels of HLA-DR and comparable levels of GARP compared to Tregs from uninfected donors. Moreover, none of these markers was significantly changed by HAART. Treg expression of CTLA-4 and cytotoxic molecules was identical between patients and controls. The most striking difference in terms of functional molecules was the high expression of CD39 by Tregs in untreated patients, which HAART just handled partly. Launch Regulatory T ...
TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental autoimmune encephalomyelitis.
Thymic derived naturally occurring CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we discuss the capacity of dendritic cells (DCs) to expand antigen-specific Tregs, particularly polyclonal Tregs directed to alloantigens. Initial studies have shown th …
The mechanisms underlying the regulation of immune activation and immune exhaustion of T cells are unclear. Tregs have been investigated in HIV-1-infected subjects with conflicting results. Our data suggest that exhausted T cells are not only associated with hyperactivated T cells but also with reduced numbers of Tregs. When we determined the CD4+CD25bright FoxP3+ Treg population in proportion to CD4+CD25bright FoxP3 negative non-Treg activated CD4 T cells, we noted that the proportions were altered in favor of the non-Treg-activated CD4 T cells in HIV-positive subjects. In this analysis, however, the changes observed in Treg frequency could have simply been a consequence of changes in activated CD4+ T-cell frequency. On the other hand, the percentage of Tregs in the total CD4+ T-cell population of the viremic patients was also significantly lower as compared with aviremic patients and to healthy controls. As activated CD8 T cells were also clearly higher in viremic patients, this provides ...
Regulatory T cells help maintain intestinal homeostasis by preventing inappropriate innate and adaptive immune responses. CD4(+) T cells that express Foxp3 and Tr1-like cells that produce IL-10 comprise the major regulatory populations in the intestine. CD4(+)Foxp3(+) T cells play an important functional role in promoting tolerance of the flora and dietary proteins. Tr1-like cells can be generated in conditions that also promote effector T cell responses and may serve a similar function. In this review, we discuss the signals specific to the gastrointestinal tract that support both regulatory cell types and their distinct modes of action in the mesenteric lymph nodes and intestinal tissues. Dysregulation of intestinal immune homeostasis occurs in inflammatory bowel disease and can also be observed in graft-versus-host disease, tumor immunotherapy regimens, and acute HIV infection.
In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers. Treg numbers, expression, and suppressive function were quantified in subjects recruited prenatally from neighborhoods where ≥ 20% of families have incomes below the poverty line. Proportion of Treg cells and expression of naïve (CD45RA) or activated (CD45RO, CD69, and HLA-DR) markers in CD4+T cells was measured by flow cytometry. Treg suppressive capacity was determined by quantifying PHA-stimulated lymphocyte proliferation in mononuclear cell samples with and without CD25 depletion. In an urban cohort of 119 newborns and 82 mothers, we found that newborns had
TY - JOUR. T1 - Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity. AU - MacConmara, Malcolm P.. AU - Maung, Adrian A.. AU - Fujimi, Satoshi. AU - McKenna, Ann M.. AU - Delisle, Adam. AU - Lapchak, Peter H.. AU - Rogers, Selwyn. AU - Lederer, James A.. AU - Mannick, John A.. PY - 2006/10/1. Y1 - 2006/10/1. N2 - OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 ± 16.3 years of age) with Injury Severity Scores (ISS) 36.6 ± 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine ...
Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3( …
Scurfy mice are deficient in regulatory T cells (Tregs), develop a severe, generalized autoimmune disorder that can affect almost every organ and die at an early age. Some of these manifestations resemble those found in systemic lupus erythematosus (SLE). In addition, active SLE is associated with low Treg numbers and reduced Treg function, but direct evidence for a central role of Treg malfunction in the pathophysiology of lupus-like manifestations is still missing. In the present study, we characterize the multiorgan pathology, autoantibody profile and blood count abnormalities in scurfy mice and show their close resemblances to lupus-like disease. Scurfy mice have dysfunctional Tregs due to a genetic defect in the transcription factor Forkhead box protein 3 (Foxp3). We analyzed skin, joints, lung and kidneys of scurfy mice and wild-type (WT) controls by conventional histology and immunofluorescence (IF) performed hematological workups and tested for autoantibodies by IF, immunoblotting and enzyme
T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-α (TNF-α). Protein kinase C-θ (PKC-θ) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-θ was sequestered away from the Treg immunological synapse. Furthermore, PKC-θ blockade enhanced Treg function, demonstrating PKC-θ inhibits Treg-mediated suppression. Inhibition of PKC-θ protected Treg from inactivation by TNF-α, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-θ-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.. ...
TY - JOUR. T1 - Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury. AU - Sakai, Ryota. AU - Ito, Minako. AU - Komai, Kyoko. AU - Iizuka-Koga, Mana. AU - Matsuo, Kazuhiko. AU - Nakayama, Takashi. AU - Yoshie, Osamu. AU - Amano, Koichi. AU - Nishimasu, Hiroshi. AU - Nureki, Osamu. AU - Kubo, Masato. AU - Yoshimura, Akihiko. N1 - Funding Information: We would like to thank Mari Ikeda, Yoshiko Noguchi, Yasuko Hirata, and Yukiko Tokifuji (Keio University) for their technical assistance; Mika Inoue (Keio University) and Kasane Imura-Kishi (The University of Tokyo) for their help in manuscript preparation; and Yuzo Koda (Keio University) for his invaluable insights. R.S. is supported by a Tadamitsu Kishimoto Kibou Projects Scholarship for Doctoral Students in Immunology. This work was supported by JSPS KAKENHI (S) JP17H06175, Challenging Research (P) JP18H05376, and AMED-CREST JP 20gm1110009 grants to A.Y.; JSPS KAKENHI 17K15667, 19H04817, and ...
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Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients
TY - JOUR. T1 - Engineered T regulatory type 1 cells for clinical application. AU - Gregori, S. AU - Roncarolo, MG. PY - 2018. Y1 - 2018. N2 - T regulatory cells, a specialized subset of T cells, are key players in modulating antigen (Ag)-specific immune responses in vivo. Inducible T regulatory type 1 (Tr1) cells are characterized by the co-expression of CD49b and lymphocyte-activation gene 3 (LAG-3) and the ability to secrete IL-10, TGF-β, and granzyme (Gz) B, in the absence of IL-4 and IL-17. The chief mechanisms by which Tr1 cells control immune responses are secretion of IL-10 and TGF-β and killing of myeloid cells via GzB. Tr1 cells, first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplantation, have been proven to modulate inflammatory and effector T cell responses in several immune-mediated diseases. The possibility to generate and expand Tr1 cells in vitro in an Ag-specific manner has led to their ...
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CD4+ T cells play key roles in the regulation of immune responses against pathogenic infectious antigens via development into effector T helper and induced regulatory T (iTreg) cells. Particularly, CD4+CD25+Foxp3+ iTreg cells are crucial for maintaining immune homeostasis and controlling inflammatory diseases. Anti-inflammatory drugs that enhance iTreg cell generation would be effective at preventing and treating inflammatory and autoimmune diseases. In this study, we examined whether anti-malarial and anti-arthritic amodiaquine (AQ) could affect iTreg cell development. Despite the anti-proliferative activity of AQ, AQ only moderately decreased iTreg cell proliferation but substantially increased IL-2 production by iTreg cells. Furthermore, AQ dose-dependently increased iTreg cell development and significantly upregulated iTreg cell markers including CD25. Interestingly, CD25 expression was decreased at later stages of iTreg cell development but was sustained in the presence of AQ, which was ...
Immune-suppressive cellular immunotherapy requires large numbers of antigen-specific regulatory T cells (Treg cells), lymphocytes that suppress certain immune responses. Together, three papers in this issue of Science Translational Medicine describe protocols for the ex vivo expansion of human Treg cells and assess the immune-suppressive function of ex vivo-manipulated Treg cells after transfer into humanized mouse disease models. Along with recent phase I clinical trial results, these new data provide a platform for clinical use of Treg cells as personalized therapeutic agents for the treatment of autoimmune diseases, graft-versus-host disease, and transplant rejection.. ...
This simple picture has been complicated by the discovery of two further contrasting lineages of cells. The IL-17-secreting and IL-22-secreting pro-inflammatory Th17 cell has been implicated in combating extracellular bacterial and fungal infections and has been linked to a number of mouse models of autoimmune disease.5 In contrast, the anti-inflammatory induced T regulatory (iTreg) cell, characterized by the expression of the transcription factor forkhead box P3, inhibits proliferation and cytokine production by other T cells.5 Despite their opposite roles, in mice, Th17 and iTreg cells are both induced by activation in the presence of the cytokine transforming growth factor beta (TGF-beta). The combination of TGF-beta with the STAT3-activating cytokine IL-6 produces a Th17 cell,6 whereas the combination of TGF-beta and the STAT5-activating cytokine IL-2 induces iTreg cell differentiation.7 The key regulating cytokines in humans are not fully understood, although many recent articles have ...
Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1cKO
Results Skewing was not associated with increased age in patients with SSc, in contrast to the control population (r=0.45, p,0.0001). Taking this into account, a significantly higher frequency of skewed XCI was found in patients with SSc compared with controls (p=0.001). No difference in skewing was observed between the immune cell subsets. In addition, a higher concentration of Foxp3+ cells exhibiting a lower Foxp3 mean fluorescence intensity was found in the patients with SSc, with profound XCI skewing (both p,0.001) associated with less efficient suppressive activity (p=0.012). ...
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation - Ontology Report - Chinchilla Research Resource Database
The evolution of immune blockades in tumors limits successful anti-tumor immunity, but the mechanisms underlying this process are not fully understood. Depletion of regulatory T cells (Tregs), a T cell subset that dampens excessive inflammatory and autoreactive responses, can allow activation of tumor-specific T cells. However, cancer immunotherapy studies have demonstrated that a persistent failure of activated lymphocytes to infiltrate tumors remains a fundamental problem. In evaluating this issue, we found that despite an increase in T cell activation and proliferation following Treg depletion there was no significant association with tumor growth rate. In contrast, there was a highly significant association between low tumor growth rate and the extent of T cell infiltration. Further analyses revealed a total concordance between low tumor growth rate, high T cell infiltration and the presence of high endothelial venules (HEV). HEV are blood vessels normally found in secondary lymphoid tissue ...
Treg-cell function is compromised in rheumatoid arthritis (RA). As the master regulator of Treg cells, FOXP3 controls development and suppressive function. Stable Treg-cell FOXP3 expression is epigenetically regulated; constitutive expression requires a demethylated Treg-specific demethylated region. Here, we hypothesised that methylation of the FOXP3 locus is altered in Treg cells of established RA patients. Methylation analysis of key regulatory regions in the FOXP3 locus was performed on Treg cells from RA patients and healthy controls. The FOXP3 Treg-specific demethylated region and proximal promoter displayed comparable methylation profiles in RA and healthy-donor Treg cells. We identified a novel differentially methylated region (DMR) upstream of the FOXP3 promoter, with enhancer activity sensitive to methylation-induced silencing. In RA Treg cells we observed significantly reduced DMR methylation and lower DNA methyltransferase (DNMT1/3A) expression compared with healthy Treg cells. Furthermore,
Experimental evidence supporting the possibility of antigen-specific Treg in atherosclerosis does exist. Atherosclerotic disease in ApoE−/− can be attenuated by adoptive transfer of HSP60-specific Treg generated in vitro by stimulation of naïve T cells with HSP60 and immature dendritic cells.13 Furthermore, induced mucosal tolerance to HSP60 reduces atherosclerosis in mice.14,15 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Van Puijvelde et al also present data demonstrating that induction of oral tolerance to HSP60 and to small HSP60-peptide significantly reduces atherosclerotic plaque size in Ldlr−/− mice.16 This study goes beyond the previous studies with similar findings by showing the tolerogenic and atheroprotective effect is related to increased Treg activity. Oral tolerance toward HSP60 in the atherosclerotic mice was associated with increased Treg numbers in lymphoid tissues, and with increased ex vivo production of IL-10 and TGF-β by T cells from the ...
Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3(+), CD4(+), and CD8(+) cytotoxic lymphocytes (CTLs) as well as CD56(+) NK cells and CD68(+) macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3(+) (FOXP3(+)) Tregs were found in intratumoural tissue. Additionally, regarding ICOS(+) FOXP3(+) Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3(+) cells. Higher Treg levels in tumour ...
A key role of Foxp3 in the development of natural T reg cells has been suggested from the molecular characterization of the scurfy mouse mutant. These mice, which suffer from a fatal lymphoproliferative disorder, harbor a mutated foxp3 gene coding for a product that lacks the forkhead domain (13). Scurfy mice receiving CD25+CD4+ T reg cells from WT mice remained virtually disease free (11). Furthermore, transduction of mutant Foxp3, lacking the forkhead domain, failed to confer suppressive activity to naive CD4+ T cells, in contrast to full-length Foxp3 (12). Thus, it is widely accepted that an intrinsic T cell failure to generate functional CD4+ T reg cells is the main cause of the fatal autoimmune disease in scurfy mice, although an additional role of the scurfy mutation in nonhematopoietic cells has been suggested (14, 15). Moreover, it remains unknown whether the mere absence of functional Foxp3+ T reg cells is sufficient to provoke the development of the scurfy phenotype or whether those ...
IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of
Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including ...
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Regulatory T cells (Tregs) can be anti-tumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients. Additionally, we investigated co-expression of immunosuppressive molecules on different Treg subsets in the TME, normal colon tissue and peripheral blood of CRC patients and healthy donors. In this preliminary study, we report that the majority of CD3+ T cells in the TME are CD4+ cells with high co-expression of PD-1/CTLA-4 and PD-1/CD39 molecules. Levels of CD4+FoxP3+Helios+ Tregs were significantly increased in the TME. Furthermore, we observed increased levels of PD-1
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0092]It was reasoned that if iDC could promote Treg cell survival, enriching the CD4+ population into CD25+ or CD25- prior to iDC priming would allow for tracking the development of Treg cells. Also, if repetitive stimulation of naive CD4+ cells by allogeneic iDC was inducing development of a regulatory-like T cell population that upregulated CD25 expression, increased CD25 expression in the CD4+CD25- enriched population over a short term coculture could be observed. CD4+CD25+ and CD4+CD25- cells were enriched from CD4+ T cells by MACS. Either CD4+CD25+ or CD4+CD25- cells with allogeneic iDCs, derived from 7 day culture of CD14+PBMCs with IL-4 and GM-CSF, were cocultured. Initially, MACS enriched a population of CD4+CD25+ cells appearing to have a uniform level of CD25 expression, as determined by flow cytometry (FIG. 1). However, over a three day time course, two major populations emerged from the original CD25+ population (FIG. 1). One population retained CD25 expression (referred to as ...
FOXP3+ regulatory T cells (Treg) control T cell activation and effector functions and are key players in immune homeostasis and self-tolerance. Given their central role in preventing autoimmune responses, Treg are considered important targets for the treatment of autoimmune inflammation and several strategies are being explored to enhance Treg numbers ... read more or function for the treatment of autoimmune disease. In addition, numerous research groups have studied the presence, phenotype and function of Treg in patients with autoimmune disease. Whether deficiencies in Treg underlie human autoimmune pathology, however, is still a subject of debate. In this thesis we investigated Treg numbers and function in patients with juvenile idiopathic arthritis (JIA), one of the most common autoimmune diseases in children, characterized by chronic inflammation of the joints. In these patients Treg from the site of inflammation can be studied, because during treatment synovial fluid is taken from inflamed ...
TY - JOUR. T1 - The progress and prospect of regulatory T cells in autoimmune diseases. AU - Zhang, Ximei. AU - Olsen, Nancy. AU - Zheng, Song Guo. PY - 2020/1/1. Y1 - 2020/1/1. N2 - Regulatory T cells (Treg) are an important immune cell population, playing a crucial role in regulating immune tolerance and preventing autoimmune diseases. These cells consist of various cell sub-populations and generally have an immunoregulatory or suppressive role against immune responses. They also have a different cell heterogeneity and each populations has own biological characteristics. Treg deficiency, reduction, instability, reduced vitality and dysfunction all account for multiple autoimmune diseases. In this review, we have systemically reviewed Treg classification, phenotypic features, regulation of Foxp3 expression, plasticity and stability of Treg as well as their relationship with several important autoimmune diseases. We particularly focus on why and how inflammatory and diet environments affect the ...
Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (Treg) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a ...
Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. CD4+CD25+Foxp3+ regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3+ T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive
In this report, we describe the unexpected finding that cetuximab-based therapy is associated with an increase in CTLA-4+Foxp3+ Treg in the circulation and in the microenvironment in treated patients with HNSCC from two independent clinical trial cohorts. Indeed, higher levels of Treg correlated with worse prognosis in cetuximab-treated patients with HNSCC, as recently seen in lung cancer after neoadjuvant chemotherapy (31). For the first time, we also show that intratumoral NK cell activation and cytotoxicity occurs during cetuximab therapy, which is primarily inhibited by Treg-derived TGFβ1, providing a mechanism for their suppressive effect and impact on clinical course of the disease. Furthermore, we demonstrated that NK cells can selectively eliminate intratumoral Treg in the presence of ipilimumab, which induces recovery of cetuximab ADCC activity from Treg suppression. Importantly, the suppressive effect of these Treg could be substantially abrogated by ipilimumab-mediated NK cell ...
Lieske, Nora Valeska; Tonby, Kristian; Kvale, Dag; Dyrhol-Riise, Anne Ma & Tasken, Kjetil (2015). Targeting tuberculosis and HIV infection-specific regulatory T cells with MEK/ERK signaling pathway inhibitors. PLOS ONE. ISSN 1932-6203. 10:e0141903(11) . doi: 10.1371/journal.pone.0141903 Fulltekst i vitenarkiv. Vis sammendrag Human regulatory T cells (Tregs) are essential in maintaining immunological tolerance and suppress effector T cells. Tregs are commonly up-regulated in chronic infectious diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection and thereby hamper disease-specific immune responses and eradication of pathogens. The MEK/ERK signaling pathway is involved in regulation of the FoxP3 transcription factor, which directs a lineage-specific transcriptional program to define Tregs and control their suppressive function. Here, we aimed to target activation of disease-specific Tregs by inhibition of the MEK/ ERK signaling pathway based on the hypothesis that ...
TY - JOUR. T1 - Regulatory T Cell Transmigration and Intravascular Migration Undergo Mechanistically Distinct Regulation at Different Phases of the Inflammatory Response. AU - Snelgrove, Sarah L.. AU - Abeynaike, Latasha D.. AU - Thevalingam, Sukarnan. AU - Deane, James A.. AU - Hickey, Michael J.. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Regulatory T cells (Tregs) play important roles in limiting inflammatory responses in the periphery. During these responses, Treg abundance in affected organs increases and interfering with their recruitment results in exacerbation of inflammation. However, the mechanisms whereby Tregs enter the skin remain poorly understood. The aim of this study was to use intravital microscopy to investigate adhesion and transmigration of Tregs in the dermal microvasculature in a two-challenge model of contact sensitivity. Using intravital confocal microscopy of Foxp3-GFP mice, we visualized endogenous Tregs and assessed their interactions in the dermal microvasculature. Four ...
Results Th17 cells were decreased in the peripheral blood of RA patients, while OA patients had surprisingly an altered ratio of CD25+Tregs and Tr1 cells in circulation. In synovial tissues Th17 cells, TFH and regulatory T cell subsets were enriched among CD4+ T cells in RA as compared to OA patients, while frequencies of Th1 cells were similar. RA patients had higher serum levels of IL-17, IL-10 and BAFF, while serum IL-21 was elevated in both RA and OA patients. Importantly, serum levels of IL-17, IL-10 and BAFF were enhanced only in patients with active RA or with detectable autoantibodies. Moreover, BAFF and IL-17 levels in synovial fluid were also higher in RA as compared to OA patients, while IL-10 concentrations were similar. B cells from synovial fluid spontaneously released high amounts of IgG in the absence of CD4+ helper T cells, and regulatory T cell subsets were unable to suppress B cell IgG production.. ...
BACKGROUND: Compared with rare CD4+CD25+ regulatory T cells (Tregs), CD4+CD25- T cells are abundant in peripheral blood. Studies have demonstrated that tumors can convert naive CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs; however, the potential application of the converted Tregs in transplant medicine has not well demonstrated.. MATERIALS AND METHODS: CD4+CD25- T cells isolated cultured for 5 d in various combinations of cell culture medium and conditioned medium from RenCa cells. Foxp3 levels were determined by flow cytometry and real-time polymerase chain reaction. BALB/c mouse mononuclear cells (responder) combined with different ratios of the converted CD4+CD25+ Tregs were co-cultured with inactivated C57BL/6 mononuclear cells (stimulator) in one-way mixed lymphocyte reaction (MLR). In addition, the converted Tregs were transferred into a mouse skin transplant model, and graft histology, survival time, and delayed-type hypersensitivity were assessed.. RESULTS: CD4+CD25- T cells cultured in ...
The CD25+CD49d- Regulatory T Cell Isolation Kit was developed for the isolation of CD4+CD25+CD49d- regulatory T cells from human PBMCs in a two-step procedure. - Italia
The CD25+CD49d- Regulatory T Cell Isolation Kit was developed for the isolation of CD4+CD25+CD49d- regulatory T cells from human PBMCs in a two-step procedure. | USA
Li N, Workman CJ, Martin SM, Vignali DA (Dec 2004). "Biochemical analysis of the regulatory T cell protein lymphocyte ... Maçon-Lemaître L, Triebel F (Jun 2005). "The negative regulatory function of the lymphocyte-activation gene-3 co-receptor ( ... molecular analysis of the negative regulatory function of lymphocyte activation gene-3". Journal of Immunology. 169 (10): 5392- ... "T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of ...
Resting B lymphocytes do not produce cytokines. After lipopolysaccharide (LPS) stimulation are produced TNFα, IL-1β, IL-10 and ... Regulatory B cells (Bregs or Breg cell) represent a small population of B cells which participates in immunomodulations and in ... Likewise, regulatory B cell subsets have also been demonstrated to inhibit Th1 responses through IL-10 production during ... Berthelot JM, Jamin C, Amrouche K, Le Goff B, Maugars Y, Youinou P (January 2013). "Regulatory B cells play a key role in ...
Ley K, Smith E, Stark MA (2006). "IL-17A-producing neutrophil-regulatory Tn lymphocytes". Immunologic Research. 34 (3): 229-42 ... May 2006). "Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells". Proceedings of the National ... Increased concentration of IL-6 alters the epidermal environment by decreasing the ability of T regulatory cells to control the ... "First in the world regulatory approval of Novartis' Cosentyx(TM) in Japan for both psoriasis and psoriatic arthritis". Novartis ...
... is a regulatory protein on B lymphocytes. The cytoplasmic tail of CD72 contains two potential immunoreceptor tyrosine- ... These features suggest a negative regulatory role for CD72. CD72 is a nonredundant regulator of B-cell development and a ...
E proteins are involved in the development of lymphocytes. They initiate transcription by binding to regulatory E-box sequences ... E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. This ... E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and ... Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology. 20: 301-22. ...
"Regulatory T‐lymphocytes mediate amyotrophic lateral sclerosis progression and survival". EMBO Molecular Medicine. 5 (1): 64-79 ... T regulatory (Treg) cells is also a safeguard against neuroinflammation, demonstrated by the evidence of inverse correlation of ... It is characterised by the activation of microglia and astrocytes, T lymphocyte infiltration, and the production of pro- ...
It is located on chromosome 1p13 and expressed in lymphocytes. It acts as a negative regulator of T-cell activation. Mutation ... This gene is the second major immune-regulatory gene related to autoimmune thyroid disease. CTLA-4 gene polymorphisms may ... It is also characterized by invasion of the thyroid tissue by leukocytes, mainly T-lymphocytes. A rare but serious complication ... Activation of cytotoxic T-lymphocytes (CD8+ T-cells) in response to cell-mediated immune response affected by helper T- ...
TNFRSF25 is also highly expressed by FoxP3 positive regulatory T lymphocytes. TNFRSF25 is activated by a monogamous ligand, ... This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. ... stimulates profound and highly specific proliferation of FoxP3+ regulatory T cells from their 8-10% of all CD4+ T cells to 35- ... the majority of T cells that regularly encounter cognate antigen are FoxP3+ regulatory T cells. Stimulation of TNFRSF25, in the ...
regulatory T-lymphocytes have a limited capability to control these cells. In the late stage, the extent of inflammation ... They are also involved in intensification of the function of regulatory T-lymphocytes and in the induction of apoptosis of ... leukocytes and lymphocytes), and red blood cells. Although some of these microvesicle populations occur in the blood of healthy ... cytotoxic T-lymphocytes, because microvesicles released from a tumor cell contain Fas ligand and TRAIL. They prevent ...
... and regulatory T lymphocytes. Thus, CCL1 mainly acts as a chemoattractant for monocytes/macrophages, T lymphocytes, specially ... CCL1 is secreted by activated monocytes/macrophages, T lymphocytes and endothelial cells. CCL1 binds to the chemokine receptor ... most likely leading to an influx of lymphocytes and monocytes and thus to an adaptive immune response. Because CCL1 binds to ... Th2-differentiated T cells and a subset of T regulatory cells in vitro into inflammatory siter. It can also attract NK cells, ...
González-Amaro R, Marazuela M (April 2016). "T regulatory (Treg) and T helper 17 (Th17) lymphocytes in thyroid autoimmunity". ... This in turn results in temporary lymphocyte retention in the lymph organs. It is thought that retention of lymphocytes in the ... is involved in lymphocyte proliferation and functions as a signal-transmitting receptor in lymphocytes, including natural ... Most lymphocytes express sphingosine-1-phosphate receptors (S1P1-5), which are G protein-coupled receptors located in the cell ...
Interleukin 10 is produced by regulatory T lymphocytes, B cells, and monocytes. It is a homodimer that functions through the IL ... is involved in immuno-regulatory responses IL-24 produced by activated monocytes and T-cells. IL-26 is a newly discovered ...
"IRF8 interferon regulatory factor 8 [Homo sapiens (human)] - Gene - NCBI". "MAP2K1 mitogen-activated protein kinase kinase 1 [ ... Shukla V, Lu R (August 2014). "IRF4 and IRF8: Governing the virtues of B Lymphocytes". Frontiers in Biology. 9 (4): 269-282. ... Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer ... These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid ...
... a set of non-B-cell lymphocytes; 2) IRF8 (10-50% of cases) which encodes the interferon regulatory factor 8 protein, a protein ... The following lymphocyte disorders may be confused with but can be distinguished from PTFL based on the following points: ... "IRF4 interferon regulatory factor 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. "IGH immunoglobulin heavy ... "IRF8 interferon regulatory factor 8 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. "MAP2K1 mitogen-activated ...
These results strongly support the regulatory role of TIRC7 signalling pathway in lymphocytes. TCIRG1 mutations affect the a3 ... Upon lymphocyte activation TIRC7 is upregulated to engage HLA-DRα2 and induce apoptotic signals in human CD4+ and CD8+ T-cells ... The negative immune regulatory role of TIRC7 is furthermore supported by the fact that TIRC7 knock out mice exhibits an ... The induction of TIRC7 in IL-10 secreting T regulatory cells and the prevention of colitis in the presence of TIRC7 positive T ...
"Entrez Gene: SIPA1 signal-induced proliferation-associated gene 1". Minato N (1997). "[Regulatory mechanisms of lymphocyte ... It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. ...
Removal of sialic acid residues from the surface of tumor cells makes them available to NK cells and cytotoxic T lymphocytes ... Below is a table that listed known PRRs and interferon regulatory factors that are getting activated upon SeV infection. SeV ... Barnes BJ, Moore PA, Pitha PM (June 2001). "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results ... The persistent infection can also be established instantly in interferon regulatory factor 3 (IRF-3)-knockdown cells. IRF-3 is ...
June 2015). "Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors". ... July 2018). "Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study". Neurology. 5 (4): ... Another regulatory T cell subset is Treg17 cells. Regulatory T cells are involved in shutting down immune responses after they ... Regulatory T cells can produce Granzyme B, which in turn can induce apoptosis of effector cells. Regulatory T cells from ...
Fanzo JC, Hu CM, Jang SY, Pernis AB (February 2003). "Regulation of lymphocyte apoptosis by interferon regulatory factor 4 (IRF ... October 1996). "Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to ... IRF4 is necessary for effector function of T regulatory cells due to its role as a regulatory factor for Blimp-1. IRF4 is an ... The expression of IRF4 is essential for the differentiation of T lymphocytes and B lymphocytes as well as certain myeloid cells ...
Later was shown that the effect of monoclonal antibodies is formation of regulatory T lymphocytes. It has been shown that ... was originally used by Gershon and Kondo in 1970 for suppression of naive lymphocyte populations by cells with regulatory ... During a tolerant state potential effector cells remain but are tightly regulated by induced antigen-specific CD4+ regulatory T ... Gershon, R. K.; Kondo, K. (May 1970). "Cell interactions in the induction of tolerance: the role of thymic lymphocytes". ...
NKT cell Journal Screening Nature glossary on murine NKT cells Nature Reviews Web Focus on regulatory lymphocytes (Webarchive ... While iNKT cells are not very numerous, their unique properties makes them an important regulatory cell that can influence how ... In addition there are subtypes specialized in T follicular helper-like function and IL-10 dependent regulatory functions. Once ... They engage in cross talk with other immune cells, like dendritic cells, neutrophils and lymphocytes. Activation occurs by ...
Regulatory B (Breg) cell An immunosuppressive B cell type that stops the expansion of pathogenic, pro-inflammatory lymphocytes ... B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral ... B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on ... No common Breg cell identity has been described and many Breg cell subsets sharing regulatory functions have been found in both ...
MDSCs can also play a positive regulatory role. It is stated that MMR vaccine stimulates MDSC populations in people taking the ... Suppressor activity of MDSC is determined by their ability to inhibit the effector function of lymphocytes. Inhibition can be ... In addition to producing NO and ROS, MDSCs secrete immune-regulatory cytokines such as TNF, TGFB, and IL10. There are ... Blidner AG, Méndez-Huergo SP, Cagnoni AJ, Rabinovich GA (November 2015). "Re-wiring regulatory cell networks in immunity by ...
"Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments". ... Oct1 is expressed in T-lymphocytes and Oct2 is induced after cell activation. NFAT has multiple family members, all of them are ... On the other hand, IL-2/JES6-1 highly selectively stimulate regulatory T cells and they could be potentially useful for ... It is a 15.5-16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are ...
Regulatory macrophages produce Interleukin 10, which can inhibit cytotoxic responses of other lymphocytes to cancer cell ... or regulatory. Regulatory-phenotype macrophages have only recently been recognized as an important contributor to tissue ... Regulatory macrophages do not fit into the M1/M2 classification system, and they display different markers. After receiving ... Similar molecules may cause development of an inhibitory, regulatory phenotype. A MAF can also alter the ability of macrophages ...
"Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family". J. ... Signal-regulatory protein gamma is a protein that in humans is encoded by the SIRPG gene. SIRPG has also recently been ... PDBe-KB provides an overview of all the structure information available in the PDB for Human Signal-regulatory protein gamma ( ... "Entrez Gene: SIRPG signal-regulatory protein gamma". Kharitonenkov A, Chen Z, Sures I, et al. (1997). "A family of proteins ...
Self antigens, in the right context, form a regulatory T-cell population that protects self tissues from immune attack or ... Alternatively, macrophages and other cytotoxic lymphocytes consume or destroy cells by apoptotic signaling and present self- ... and B-lymphocytes). Normally, these APC 'present' class II receptor/antigens to a great many T-cells, each with unique T-cell ...
"Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine ... protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis". Blood. 104 (1): 215-23. doi:10.1182/blood-2003-12-4295 ...
... on T lymphocytes: activation-dependent up-regulation and regulatory function". Eur. J. Immunol. 31 (4): 1173-80. doi:10.1002/ ... Together, CR3 and CR4 are involved in various functions of the T and B lymphocytes and NK cells. For instance, while both CR3 ... is a human cell surface receptor found on B and T lymphocytes, polymorphonuclear leukocytes (mostly neutrophils), NK cells, and ...
Many regulatory processes can lead to allelic exclusion. In one instance, one allele of the gene can become transcriptionally ... This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each ... This is significant as the co-expression of both alleles in B lymphocytes is associated with autoimmunity and the production of ... mature B lymphocyte to express only one type of immunoglobulin. This subsequently results in each B lymphocyte being able to ...
The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, ... Madani N, Kabat D (Dec 1998). "An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the ... Thus, 19S regulatory particle pertains a series of important capabilities to address these functional challenges. To recognize ... 26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory ...
B and T lymphocytes are tested for their affinity for self MHC/peptide complexes before leaving the primary lymphoid organs and ... there are mechanisms in the periphery involving T regulatory cells to prevent the host from obtaining an autoimmune disease. ... B lymphocytes can also participate in light chain receptor editing, VH gene replacement, or be released and later undergo ... There is a large diversity of epitopes recognized and, as a result, it is possible for some B and T lymphocytes to develop with ...
"BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non- ... a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes". J. ...
1999). "Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune ... "The death effector domain-associated factor plays distinct regulatory roles in the nucleus and cytoplasm". J. Biol. Chem. ...
A low level of blood lymphocytes may result from the virus acting through ACE2-related entry into lymphocytes. Another common ... The first COVID‑19 vaccine was granted regulatory approval on 2 December 2020 by the UK medicines regulator MHRA. It was ... Autopsies of people who died of COVID‑19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates ...
This regulatory pathway was new at the time and not well understood. One of its advantages is that the US FDA holds more ... It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It works by targeting the cellular pathway of ... This was Merck's first use of the designation and the reduction in regulatory risk was one of the reasons management was ... Pembrolizumab is a therapeutic antibody that binds to and blocks PD-1 located on lymphocytes. This receptor is generally ...
Liu FT (April 2005). "Regulatory roles of galectins in the immune response". International Archives of Allergy and Immunology. ... is a novel eosinophil chemoattractant produced by T lymphocytes". The Journal of Biological Chemistry. 273 (27): 16976-84. doi: ...
Cantor's early studies focused on the development and function of lymphocytes derived from the thymus (T-lymphocytes or T cells ... Hu D, †Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H. Analysis of regulatory CD8 cells in mice deficient in the Qa-1 ... Nature 2010;467:328 Kim, H-J, Wang X, Radfar S, Sproule TJ, Roopenian DC, Cantor H. CD8+ T regulatory cells express the Ly49 ... Nabel G, Fresno M, Chessman A, Cantor H. Use of cloned populations of mouse lymphocytes to analyze cellular differentiation. ...
UBL regulatory systems - including UBLs themselves and the cascade of enzymes that interact with them - are believed to share a ... "Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living ... These chains may be linear or branched, and different regulatory signals may be sent by differences in the length and branching ... The evolution of UBLs and their associated suites of regulatory proteins has been of interest since shortly after they were ...
These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the ... Madani N, Kabat D (Dec 1998). "An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the ... The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP ... Ben-Neriah Y (Jan 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20-6. doi: ...
... discovery of regulatory T cells Louis W. Sauer (1885-1980), perfected pertussis vaccine, developed diphtheria/p daertussis/ ... who established that dendritic cells are responsible for imprinting the tissue-specific homing of T lymphocytes Fred Rosen ( ...
It is associated with agammaglobulinemia-6. The B lymphocyte antigen receptor is a multimeric complex that includes the antigen ... immunoglobulin-like regulatory regions, and allelic polymorphism". Immunogenetics. 40 (2): 145-9. doi:10.1007/BF00188178. PMID ... "Entrez Gene: CD79B CD79b molecule, immunoglobulin-associated beta". Reth M (1992). "Antigen receptors on B lymphocytes". Annu. ... and serine phosphorylation of the p56lck protein tyrosine kinase in response to antigen receptor cross-linking in B lymphocytes ...
Due to the AP-1 regulatory functions in cancer cells, AP-1 modulation is studied as a potential strategy for cancer prevention ... Martins G, Calame K (2008). "Regulation and functions of Blimp-1 in T and B lymphocytes". Annual Review of Immunology. 26: 133- ... AP-1 was first discovered as a TPA-activated transcription factor that bound to a cis-regulatory element of the human ... Since its discovery, AP-1 has been found to be associated with numerous regulatory and physiological processes, and new ...
... gene regulatory network - genetic carrier - genetic code - genetic drift - genetic engineering - genetic fingerprint - genetic ... lymphocyte homing receptor - lysine - lysis - lysis buffer - lysozyme - lytic cycle macroevolution - macromolecular system - ... nucleic acid regulatory sequence - nucleic acid repetitive sequence - nucleic acid sequence homology - nucleon - nucleophile - ...
Nonetheless, regulatory bodies, such as the Nuclear Regulatory Commission (NRC), commonly use LNT as a basis for regulatory ... November 2011). "Chromosome aberrations in peripheral blood lymphocytes of individuals living in high background radiation ... The LNT model is commonly used by regulatory bodies as a basis for formulating public health policies that set regulatory dose ... The NRC upheld the LNT model in 2021 as a "sound regulatory basis for minimizing the risk of unnecessary radiation exposure to ...
These studies have had a broad impact on the development, evaluation and regulatory approval of drugs, and helped to establish ... These observations have raised fundamental questions about T lymphocyte biology and viral replication that bridge to a basic ...
El Mir, S.; Triebel, F. (2000-06-01). "A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits ... Type 1 regulatory cells or Tr1 (TR1) cells are a class of regulatory T cells participating in peripheral immunity as a subsets ... IL-27, together with TGF-β induces IL-10-producing regulatory T cells with Tr1-like properties cells. IL-27 alone can induce IL ... In vivo Tr1 cells need to be activated, to be able to exert their regulatory effects. Cytokines mediated Tr1 cells secrete ...
Recent research demonstrates that reduction of lymphocyte populations can impair cognition in mice, and that restoration of ... from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response ... lymphocytes restores cognitive abilities. Epigenetic medicine encompasses a new branch of neuroimmunology that studies the ...
Lymphocytes can enter mitosis when they are activated by mitogens or antigens. B cells specifically can divide when they ... TGF-𝝱 works by binding to cell-surface receptors and activating the Smad gene regulatory proteins. Smad proteins then trigger ... T cells undergo mitosis when stimulated by mitogens to produce small lymphocytes that are then responsible for the production ... Mitogens are often used to stimulate lymphocytes and thereby assess immune function. The most commonly used mitogens in ...
Maternal immune factors are transferred by lymphocytes traveling from the mother's gut to the mammary gland where the secretory ... "Immune regulatory cytokines in the milk of lactating women from farming and urban environments". Pediatric Allergy and ... Their presence in human milk may stimulate lymphocytes responsible for the development of the infant's specific immunity. ...
The table below shows some transcription factors that have been predicted by Genomatix that binds to the regulatory sequence of ... through GEO profiles show that CCDC138 is expressed in moderate levels in various tissues including peripheral blood lymphocyte ...
B lymphocytes (B cells), which are part of the normal immune response, are also responsible for the over-aggressive response ... Regulatory agencies recommend that patients be treated with an antihistamine prior to a belimumab infusion. Because belimumab ... B-cell activating factor (BAFF), also called B-lymphocyte stimulator (BLyS), is required for the development and survival of B ... It interacts with three membrane receptors on B lymphocytes: BAFF-R (BAFF receptor) BCMA (B cell maturation antigen) TACI ( ...
Winoto A, Littman DR (April 2002). "Nuclear hormone receptors in T lymphocytes". Cell. 109 Suppl (2): S57-S66. doi:10.1016/ ... "Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element". The ... Expression is inducible by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. ...
Müller-Suur, C.; Larsson, K.; Malmberg, P.; Larsson, P.H. (1997). "Increased number of activated lymphocytes in human lung ... Appendix to EPA ICR 1989.06: Supporting Statement for the Information Collection Request for NPDES and ELG Regulatory Revisions ... through regulatory change enacted by the Food and Drug Administration (FDA), which sought voluntary compliance from drug ...
CDK5 regulatory subunit associated protein 1 like 1 (6p22.3) COL11A2: collagen, type XI, alpha 2(6p21.3) CYP21A2: cytochrome ... LY6G6E encoding protein Lymphocyte antigen 6 complex, locus G6E (pseudogene) (6p21.33) MIR4640: microRNA 4640 (6p21.33) MLIP: ...
... and STAT6 determines the levels of CD20 on the surface of normal and malignant B lymphocytes. STAT6 also plays a critical role ... "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine ... "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine ...
CD8+ T cells and CD8+ tumor infiltrating lymphocytes (TILs) from individuals with melanoma. Blockade of TIGIT and PD-1 led to ... "TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity". Nature Communications. 9 (2858): 2858. Bibcode ...
You M (October 2020). "Changes of China's regulatory regime on commercial artificial breeding of terrestrial wildlife in time ... or CD4+ T-lymphocyte deficiency. Pets may also serve as a reservoir of viral disease and contribute to the chronic presence of ...
Liu L, Zhang J, Yuan J, Dang Y, Yang C, Chen X, Xu J, Yu L (March 2005). "Characterization of a human regulatory subunit of ... In this way, it governs the action of cytotoxic lymphocytes. The amount of IL-2 being produced by the T-helper cells is ... IL-2 activates T-helper lymphocytes and induces the production of other cytokines. ... calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, ...
The pre-mRNA of this protein is edited in many tissues( heart, bladder, lymphocytes, fibroblast, epithelial cells and brain) ... ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory ... It is widely expressed protein but expression is particularly high in brain and B lymphocytes. Alternative promoters and ...
Over-expression of CD200 un acute myeloid leukemia mediates the expansion of regulatory T-lymphocytes and directly inhibits ... Over-expression of CD200 un acute myeloid leukemia mediates the expansion of regulatory T-lymphocytes and directly inhibits ...
... a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown ... a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown ... Lymphocyte Subsets Separation. Peripheral T-lymphocytes were separated from PBMCs by immunomagnetic depletion of non-CD3+ cells ... miR-29a-3p/T-bet Regulatory Circuit Is Altered in T Cells of Patients With Hashimotos Thyroiditis. Stana Tokić1,2*†, Mario ...
T1 - The Regulatory Role of Macrophages in Antigenic Stimulation Part Two. T2 - Symbiotic Relationship between Lymphocytes and ... title = "The Regulatory Role of Macrophages in Antigenic Stimulation Part Two: Symbiotic Relationship between Lymphocytes and ... The Regulatory Role of Macrophages in Antigenic Stimulation Part Two: Symbiotic Relationship between Lymphocytes and ... The Regulatory Role of Macrophages in Antigenic Stimulation Part Two: Symbiotic Relationship between Lymphocytes and ...
B Lymphocytes. Under the influence of IL-4, IL-13 and IL-9, B cells generate IgE in the draining lymph nodes, in the mucosal ... lymphoid tissue or at the site of inflammation.[45] They may also function as APCs or may play a regulatory role through ...
Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and ... 2. Roles of Negative Regulatory T Cell Co-Receptors. 2.1. Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4). Cytotoxic T-lymphocyte ... Wolf, I.M.A.; Guse, A.H. Ca2+ microdomains in T-lymphocytes. Front. Oncol. 2017, 7, 73. [Google Scholar] [CrossRef] [PubMed] ... Zhao, C.; Davies, J.D. A peripheral CD4+ T cell precursor for naive, memory, and regulatory T cells. J. Exp. Med. 2010, 207, ...
Resting B lymphocytes do not produce cytokines. After lipopolysaccharide (LPS) stimulation are produced TNFα, IL-1β, IL-10 and ... Regulatory B cells (Bregs or Breg cell) represent a small population of B cells which participates in immunomodulations and in ... Likewise, regulatory B cell subsets have also been demonstrated to inhibit Th1 responses through IL-10 production during ... Berthelot JM, Jamin C, Amrouche K, Le Goff B, Maugars Y, Youinou P (January 2013). "Regulatory B cells play a key role in ...
... Curr Opin Immunol. 2017 Apr;45:8-15. doi: ... Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive ... programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating ...
Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties  Alobaid, Meshal ( ... Dataset contains raw and processed data used for the creation of figures in publication "Developing immune-regulatory materials ... Browsing public research data by Subject "T-Lymphocytes". 0-9. A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P. Q. R. S. T. U. V ...
... which provide valuable but insufficient information for the inference of regulatory interactions. Here we present a ... Genome-Wide Discovery of Modulators of Transcriptional Interactions in Human B Lymphocytes. *Kai Wang, I. Nemenman, N. Banerjee ... Reverse engineering of regulatory networks in human B cells. *K. Basso, A. Margolin, G. Stolovitzky, U. Klein, R. Dalla-Favera ... Gene Regulatory Network Inference from Single-Cell Data Using Multivariate Information Measures. *Thalia E. Chan, M. Stumpf, A ...
CD4+ cells are divided further into T helper (Th)1, Th2, Th17 and regulatory T (Treg) subsets, while CD8+ cells are divided ... The lymphocytes were prepared using a lymphocyte kit (Lymphoprep™ Axis-Shield PoC AS, Oslo, Norway). The peripheral blood ... In total, in the control group, the percentage of CD3+, CD3+CD8− and CD3+CD8+ T lymphocyte subset cells were 61.60±4.61, 43.01± ... T lymphocytes are considered to be crucial cells in the regulation of the immune system (16). Based on the receptors on T ...
... , T-Cell, T-Cell Activation, T-Cell Surface Receptor, T-Helper Cell, Helper T-Cell, CD4+ Cell, T-Cytotoxic Cell, ... T Suppressor Cells (Regulatory T Cells). *Suppress immune cell activation. *Prevents autoimmune reactions by promoting self ... t lymphocyte, t cells, t lymphocytes, t-lymphocytes, t-lymphocyte, t-cell, T Cell Lymphocyte, T lymphocyte, T cell, T-cell, T ... LYMPHOCYTES J, lymphocytes T cells, thymus-dependent lymphocyte, lymphocytes T cells (lab test), T cells, T-lymphocyte, thymus ...
2011) β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system The ... Our study suggests that it may be the CNS regulatory machinery that is dysfunctional, which could be partially restored by ... In the later stage, the levels of many more cytokines produced by macrophages and/or lymphocytes were significantly decreased, ... Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and ...
Functional studies of T regulatory lymphocytes in human schistosomiasis in Western KenyaExternal. Ondigo BN, Ndombi EM, ... We now report that the removal of Treg (CD4+/CD25(hi)/CD127(low) lymphocytes) from peripheral blood mononuclear cells (PBMCs) ... Immunoregulation is considered a common feature of Schistosoma mansoni infections, and elevated levels of T regulatory (Treg) ... lymphocytes have been reported during chronic human schistosomiasis. ...
Early self-regulatory mechanisms control the magnitude of CD8+ T cell responses against liver stages of murine malaria. J. ... Chakravarty, S., Cockburn, I., Kuk, S. et al. CD8+ T lymphocytes protective against malaria liver stages are primed in skin- ... CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. *Sumana Chakravarty1, ... Parasites remain in the liver for only a short duration and there may not be sufficient time to recruit lymphocytes from other ...
The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, ... T and B lymphocytes); and cells from the surrounding stroma that are recruited to the tumor site (consisting of fibroblasts, ... The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, ... The Tumorigenic Roles of the Cellular REDOX Regulatory Systems. Stéphanie Anaís Castaldo. ,1Joana Raquel Freitas. ,1Nadine ...
T regulatory lymphocytes ; 5T4 ; CTLA4 ; tremelimumab ; oesophageal cancer ; gastric cancer ; cancer immunotherapy ... Markers of regulatory phenotype, forkhead box protein 3 (FoxP3) and CTLA4, doubled transiently in CD4+CD25high lymphocytes in ... T regulatory lymphocytes ; 5T4 ; CTLA4 ; tremelimumab ; oesophageal cancer ; gastric cancer ; cancer immunotherapy ... a key negative regulator of T cell activation found on dedicated regulatory T cells (Treg) and activated T lymphocytes, and ...
Bare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined ... The RFX5, RFXANK, and RFXAP proteins come together to form the regulatory factor X (RFX) complex, which attaches (binds) to ... Genetic Testing Registry: Bare lymphocyte syndrome type 2, complementation group A *Genetic Testing Registry: Bare lymphocyte ... which leads to an absence of MHC class II proteins on the surface of certain lymphocytes. Lack of these proteins on lymphocytes ...
... the role of different T cell populations in CRC and understand how Treg influence local anti-tumor immunity and lymphocyte ... The ability of regulatory T cells to influence lymphocyte recruitment and T cell effector functions in the tumor ... and the most important cell types for anti-tumor immunity are cytotoxic and cytokine producing lymphocytes. These lymphocytes ... Regulatory T cells (Treg), on the other hand, can inhibit the function of cells with anti-tumor activity and thereby help the ...
Regulatory T lymphocytes; macr: Macrophage; M1-M2 macr. shift: Macrophage shift from M1 pro-inflammatory phenotype to M2 anti- ... REGULATORY STATUS. From a regulatory standpoint, stem cells are regulated both in Europe and United States under specific ... Several MSC-driven mechanisms concur to orientate activated lymphocytes toward the T-regulatory phenotype. TSG-6 enhances ... Inhibition of effector lymphocytes through IL-10. [13,17]. PGE2. X. X. X. Macrophage conversion to M2 phenotype, NK cell ...
T cells are a type of lymphocyte. Lymphocytes are a type of white blood cell. They make up part of the immune system. T cells ... Change in frequency of peripheral regulatory T cells baseline treatment up to 6 weeks. ...
T-Lymphocytes, Regulatory. Ehrlich AK, Pennington JM, Tilton S, Wang X, Marshall NB, Rohlman D, Funatake C, Punj S, ODonnell E ...
Optimizing Genetically Engineered Lymphocytes for Immunotherapy of Pediatric Sarcoma via Blockade of Negative Regulatory ... Activated human lymphocytes will be added to vector-coated plates in cAIM-V plus rIL-2 and cultured overnight. Transduction ... We propose to enhance the efficacy of these T-cells by blocking the negative regulatory axis PD1-PDL1. These studies may not ... Targeting of G(D2)-positive tumor cells by human T lymphocytes engineered to express chimeric T-cell receptor genes. Int J ...
Regulatory T cells (Treg) regulate immune responses by sup ... Cytotoxic T lymphocyte-associated antigen 4 plays an essential ... Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases ... IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+ ... Induction of tolerance in type 1 diabetes via both CD4+CD25+ T regulatory cells and T regulatory type 1 cells ...
Isolation of human regulatory T lymphocytes by fluorescence-activated cell sorting. In: Immunological Tolerance., Vol. 1899. ... Isolation of human regulatory T lymphocytes by fluorescence-activated cell sorting. In: Immunological Tolerance., Vol. 1899. ... Homing of regulatory T cells to human skin is important for the prevention of alloimmune-mediated pathology in an in vivo ... Homing of regulatory T cells to human skin is important for the prevention of alloimmune-mediated pathology in an in vivo ...
Regulatory T cells; B. NLR; C. Lymphocyte count; D. SUV. Abbreviations: NSCLC = non-small cell lung cancer; NLR = neutrophil/ ... Figure 1: The proportions of lymphocyte subsets in NSCLC patients. A. Increased regulatory T cells in NSCLC-D and NSCLC-R; ... neutrophil/lymphocyte ratio; PLR: platelet/lymphocyte ratio; MLR: monocyte/lymphocyte ratio. ... Liu C, Huang Z, Wang Q, Sun B, Ding L, Meng X, Wu S. Usefulness of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ...
  • The interaction of DCs with T-lymphocytes takes place via a multi-molecular immune synapse starting with antigen presentation via MHC class I/II on DCs to the TCR of T-lymphocytes. (medscape.com)
  • Depending upon the antigen encountered and cytokine presence, T-lymphocytes may differentiate into Th1, Th2, Th9, Th17, Th22 or Tregs for appropriate immune response. (medscape.com)
  • The presentation of antigen bound to live macrophages to the lymphocytes was a highly efficient mode of generating an immune response. (wustl.edu)
  • The cellular response is mainly a lymphocyte-mediated reaction, whereas the humoral response includes production of antibodies against the antigen by the plasma cells. (medscape.com)
  • Immunoglobulins (Igs), the term is sometimes used interchangeably with "antibodies," are glycoprotein molecules produced by B lymphocytes and plasma cells in response to an immunogen or after recognition of specific epitopes on the antigen. (medscape.com)
  • Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca 2+ signaling and promote T cell survival. (mdpi.com)
  • This project focused on cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T cell activation found on dedicated regulatory T cells (Treg) and activated T lymphocytes, and asked whether modulation of immune control with anti-CTLA4 blockade led to significant anti-tumour activity. (bl.uk)
  • DR3 is expressed preferentially by activated and antigen-experienced T lymphocytes. (miltenyibiotec.com)
  • This product is intended for in vitro diagnostic use to identify human cells expressing CD4 antigen molecules in countries where the regulatory approval has been obtained from the local regulatory authorities. (cytekbio.com)
  • The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis. (spandidos-publications.com)
  • In this study, we investigated the predictive roles of lymphocyte subsets on tumor progression in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy, and their expression in NSCLC patients at first relapse. (oncotarget.com)
  • Methods: We enrolled 70 NSCLC patients and 14 age- and sex-matched healthy donors and tested the lymphocyte subsets in their peripheral blood by flow cytometry. (oncotarget.com)
  • 30 patients at first relapse were included to evaluate the differences of lymphocyte subsets between them and first diagnosed patients and healthy volunteers. (oncotarget.com)
  • My colleagues and I are now exploring whether subsets of regulatory T cells generated in and outside of the thymus play a role in different types of cancer. (sloankettering.edu)
  • Like T cells there are many subsets of B cells with specialised functions including regulatory functions that control the immune response. (babraham.ac.uk)
  • T cells are a type of lymphocyte. (clinicaltrials.gov)
  • Each type of lymphocyte interacts with other white blood cells to mount an immune response. (babraham.ac.uk)
  • Another B7 family member ICOS present on T-lymphocytes together with ICOS-L on DCs regulate cytokine production, airway inflammation, smooth muscle cell constriction and mucus production from goblet cells. (medscape.com)
  • Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype. (nih.gov)
  • Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. (spandidos-publications.com)
  • Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. (spandidos-publications.com)
  • To help the body recognize and fight infections, MHC class II proteins on lymphocytes bind to fragments of proteins (peptides) from foreign invaders so that other specialized immune system cells can interact with them. (medlineplus.gov)
  • When these immune system cells recognize the peptides as harmful, they trigger the lymphocytes to launch immune responses to get rid of the foreign invaders. (medlineplus.gov)
  • These lymphocytes include conventional CD8+ cytotoxic T cells, NK cells, and Th1 cells, and also unconventional T cells like mucosa-associated invariant T (MAIT) cells and γ/δ T cells. (gu.se)
  • Regulatory T cells (Treg), on the other hand, can inhibit the function of cells with anti-tumor activity and thereby help the tumor to escape immune recognition. (gu.se)
  • The ability of regulatory T cells to influence lymphocyte recruitment and T cell effector functions in the tumor microenvironment is determined, and we also perform long-term follow up of patient outcome related to the immunological parameters that we characterize. (gu.se)
  • Change in frequency of peripheral regulatory T cells baseline treatment up to 6 weeks. (clinicaltrials.gov)
  • Regulatory T cells (Treg) regulate immune responses by suppressing effector T cells. (diabetesjournals.org)
  • Results: Increased proportions of regulatory T cells, CD8+ T cells, and CD8+CD28- T cells and decreased CD4+ T cells and CD4/CD8 ratios were observed in NSCLC patients at first relapse compared to newly diagnosed patients. (oncotarget.com)
  • In the 40 first diagnosed patients undergoing radiotherapy, uni- and multivariate analyses showed that increased level of regulatory T cells correlated with poor progression-free survival (hazard ratio = 2.55 and 3.76, P = 0.022 and 0.010, respectively). (oncotarget.com)
  • Conclusions: Peripheral regulatory T cells were increased and independently predict tumor progression in NSCLC patients undergoing radiotherapy, suggesting the promising combination of radiotherapy and immunotherapy. (oncotarget.com)
  • The autoimmune nature of diabetes and the major contribution of lymphocyte T-cells are well established. (who.int)
  • The discovery hinges on a population of rare immune cells called regulatory T lymphocytes, or Tregs. (thenakedscientists.com)
  • Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Poly. (thenakedscientists.com)
  • This report is the first to describe the administration of recombinant interleukin-7 to humans and demonstrates the ability of this cytokine to mediate selective increases in CD4 and CD8 lymphocytes along with a decrease in the percentage of CD4 T-regulatory cells. (elsevier.com)
  • and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells. (pasteur.fr)
  • The mammary and intestinal tumor development as well as the increase in proinflammatory mediators is suppressed by adoptive transfer of interleukin 10-competent CD4 + CD45RB lo CD25 + regulatory (T R ) cells. (aacrjournals.org)
  • Recent advances in our understanding of the pathogenesis of psoriasis identify the imbalance between CD4+ T effector cells, particularly the T helper (Th) 17 subset, and regulatory T cells (Treg) as key to the development of psoriatic lesions, and therefore a novel therapeutic target. (elsevier.com)
  • This is the pre-peer reviewed version of the following article: Kotb, I. , Lewis, B. , Barker, R. and Ormerod, A. (2018), Differential effects of phototherapy, adalimumab and betamethasone-calcipotriol on effector and regulatory T cells in psoriasis. (elsevier.com)
  • The alternative splicing of DR3 in B and T cells encounters a programmed change upon T cell-activation, which predominantly produces full-length, membrane-bound isoforms, and is thought to be involved in controlling lymphocyte proliferation induced by T cell-activation. (miltenyibiotec.com)
  • Alexander Rudensky's research focuses on the role of a subset of white blood cells called regulatory T cells, which are believed to suppress the immune system's ability to fight tumors. (sloankettering.edu)
  • His laboratory studies the development of white blood cells called T lymphocytes, which play a key role in the immune system's response to infection. (sloankettering.edu)
  • Dr. Rudensky's own research focuses on a subset of T lymphocytes called regulatory T cells. (sloankettering.edu)
  • My laboratory studies T lymphocytes , white blood cells that are vital in the immune system's response to infection. (sloankettering.edu)
  • One of the areas we focus on is a subset of T lymphocytes called regulatory T cells. (sloankettering.edu)
  • We've found that regulatory T cells are critical for keeping other white blood cells in check, thereby playing an important role in controlling immune system reactions. (sloankettering.edu)
  • In the absence of regulatory T cells, instead of attacking foreign cells, the immune system attacks normal cells and tissues, which may lead to sometimes fatal inflammatory responses. (sloankettering.edu)
  • For example, numerous studies have shown that most tumors are infiltrated by regulatory T cells, which are believed to suppress immune responses to cancer. (sloankettering.edu)
  • Previously, we and others found that a gene called Foxp3 plays a critical role in the generation of regulatory T cells both in and outside of the thymus, a small organ located underneath the breastbone. (sloankettering.edu)
  • In a series of recent studies, we reported that a distinct DNA element within the Foxp3 gene is essential for the process by which extrathymic regulatory T cells - those regulatory T cells that are generated outside of the thymus - mature and acquire specialized traits and functions. (sloankettering.edu)
  • Our findings suggest that extrathymic development of regulatory T cells emerged during evolution to prevent a mother's immune system from attacking the fetus. (sloankettering.edu)
  • In mice that lack the aforementioned Foxp3 DNA element, extrathymic regulatory T cells do not develop normally, causing pregnant females to lose their embryos more frequently and develop complications reminiscent of those seen in human pregnancies. (sloankettering.edu)
  • In another study , published in Nature in February 2012, we found that extrathymic regulatory T cells control allergic and asthma-like inflammation in the gut and lungs. (sloankettering.edu)
  • Working with Memorial Sloan Kettering Cancer Center clinicians, we are now starting to apply our knowledge about the ways regulatory T cells control multiple body functions to practical use. (sloankettering.edu)
  • We are investigating the basic biology of how lymphocytes develop into fully-fledged immune cells and signal to each other and to other cell types in the body. (babraham.ac.uk)
  • The development of skin sensitization is associated with, and requires, the activation and clonal expansion of allergen responsive T lymphocytes and it is these cells that orchestrate the cutaneous allergic reaction. (cdc.gov)
  • We tested whether the low therapeutic outcome might be due to CD4 + CD25 + regulatory T cells (Treg) present in TS/A-pc tumors and draining lymph nodes and whether IL-21 had any effect on these cells. (elsevier.com)
  • IL-21R expression on CD25 - lymphocytes suggested that IL-21 could be more effective in mice depleted of CD25 + cells. (elsevier.com)
  • Data show that BACH2 and STAT5B are activated by viral insertions, generating chimeric mRNAs specifically enriched in T regulatory cells favoring their persistence. (cusabio.com)
  • Background: Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. (diamond.ac.uk)
  • They regulate self-reactive T cells by inducing anergy and clonal deletion and/or by expanding regulatory T cells ( 1 ). (aai.org)
  • The most important aspect of the platform is that it should allow for dendritic cells to recruit T lymphocytes and induce Th1 cell polarization that if feasible will also induce a cytotoxic T cell response and thus clearance of SARS-CoV-2 virus. (pharma-industry-review.com)
  • Touch imprints from one tumor revealed positive cytoplasmic staining for IgM-K and IgM-L in medium-sized lymphocytes, but not in tumor cells. (jamanetwork.com)
  • The greatest province of these APCs is to mete out these peptide-MHC complexes to T-lymphocytes (T-cells), an impor- tant component of the adaptive untouched system. (daubnet.com)
  • Unanue, ER 1981, ' The Regulatory Role of Macrophages in Antigenic Stimulation Part Two: Symbiotic Relationship between Lymphocytes and Macrophages ', Advances in Immunology , vol. 31, no. (wustl.edu)
  • Immune responses influence patient outcome in most cancer types, and the most important cell types for anti-tumor immunity are cytotoxic and cytokine producing lymphocytes. (gu.se)
  • In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. (spandidos-publications.com)
  • In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)‑γ and interleukin (IL)‑17A. (spandidos-publications.com)
  • A subset of T-lymphocytes that are present in large numbers at MUCOUS MEMBRANES and respond to INFECTIONS . (bvsalud.org)
  • This study was undertaken to analyze tumor- infiltrating lymphocytes (TILs) in the core of the tumor and in the peripheral blood of patients with non-small cell lung cancer (NSCLC) subjected to surgery. (ersjournals.com)
  • During this time period, peripheral blood samples (n = 21) collected at each cycle of T cell immunotherapy were analyzed for circulating tumor DNA (ctDNA) mutations, TCR repertoire and T lymphocyte phenotype. (researchsquare.com)
  • The results of this study, the design of which was agreed upon with the FDA prior to its conduct, indicate that no chromosomal aberrations were induced in peripheral blood lymphocytes when Treximet was administered to volunteers for seven days. (salesandmarketingnetwork.com)
  • Immune responses influence patient outcome in most cancer types, and the aim of Marianne Quiding-Järbrink's research is to elucidate the role of different T cell populations in CRC and understand how Treg influence local anti-tumor immunity and lymphocyte recruitment to tumors. (gu.se)
  • The aim of our project is to elucidate the role of different T cell populations in colorectal carcinoma and understand how Treg influence local anti-tumor immunity and lymphocyte recruitment to tumors. (gu.se)
  • By contrast, masons had a lower percentage of CD25-positive lymphocytes (12.4 vs 20.4, p=0.01). (cdc.gov)
  • IRF9 is an important regulatory factor within the JAK-STAT signaling pathway, associated with cell immunity and other homeostatic processes. (unl.edu)
  • Chronic lymphocytic leukemia is common in adults, as it happens when bone marrow damaged lymphocytes which causes dysfunctional in production of antibodies and ultimately lost the ability to fight against infections. (databridgemarketresearch.com)
  • Consid- (for biopsy taking), pathologist (for bi- clonal proliferations of lymphocytes. (who.int)
  • [ 111 ] Conversely, it is a negative regulator of the T-lymphocyte activation and helps in the development of tolerance. (medscape.com)
  • Baseline interleukin-2 release after T lymphocyte activation was higher in patients with clinical benefit and toxicity. (bl.uk)
  • We use a multidisciplinary approach to investigate the receptors and pathways that regulate lymphocyte development and activation. (babraham.ac.uk)
  • Tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) is an interesting costimulatory molecule associated with T lymphocyte activation, and it mainly exerts its biological effects by binding to its receptors herpesvirus invasion mediator (HVEM) and lymphotoxin-ß receptor. (bvsalud.org)
  • The Epstein-Barr virus has been known to persist in latency in B lymphocytes and regulate complex cellular regulatory networks. (unl.edu)
  • We aim to understand the processes that regulate the development, survival and function of lymphocytes and also work to identify how to mitigate the effects of age on the immune system. (babraham.ac.uk)
  • [ 3 ] The clonality of the B-lymphocytes must be confirmed with flow cytometry. (medscape.com)
  • Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by a progressive proliferation and accumulation of mature yet functionally incompetent lymphocytes. (medscape.com)
  • Diverse populations of functionally mature but naive lymphocytes are generated in the absence of foreign Ags in the primary lymphoid organs (thymus, fetal liver, and bone marrow). (aai.org)
  • Markers of regulatory phenotype, forkhead box protein 3 (FoxP3) and CTLA4, doubled transiently in CD4+CD25high lymphocytes in the first month after tremelimumab before returning to baseline. (bl.uk)
  • More specifically, we are studying the expression of endothelial adhesion molecules and chemokines in unaffected and tumor tissues, and how these shape the repertoire of tumor-infiltrating lymphocytes. (gu.se)
  • Trx peroxidases, GSH peroxidases, catalase, and SOD) as well as REDOX regulatory systems that recycle/reactivate the ROS scavenging proteins and other REDOX sensitive proteins (e.g. (hindawi.com)
  • The RFX5, RFXANK, and RFXAP proteins come together to form the regulatory factor X (RFX) complex, which attaches (binds) to specific regions of DNA involved in the regulation of MHC class II gene activity. (medlineplus.gov)
  • Mutations in the CIITA , RFX5 , RFXANK , or RFXAP gene prevent transcription of MHC class II genes, which leads to an absence of MHC class II proteins on the surface of certain lymphocytes. (medlineplus.gov)
  • Lack of these proteins on lymphocytes impairs the body's immune response to bacteria, viruses, and fungi, leading to persistent infections in individuals with BLS II syndrome. (medlineplus.gov)
  • The CD4 molecule is expressed predominantly on thymocytes and a subpopulation of mature T-helper lymphocytes. (cytekbio.com)
  • Antibodies can be found on the surface of lymphocytes as an integral part of the cell membrane protein or can be freely circulating in the blood or be part of one of the body's gland secretion. (medscape.com)
  • This work proposes a relevance network model for gene regulatory network inference which employs both mutual information and conditional mutual information to determine the interactions between genes and proposes a conditional mutual Information estimator based on adaptive partitioning which allows us to condition on both discrete and continuous random variables. (semanticscholar.org)
  • This work aims to investigate whether scalable information based methods and more explicit dynamical models (like Inferelator 1.0) prove synergistic when combined and whether these can be combined to resolve the directionality of regulatory interactions. (semanticscholar.org)
  • The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. (hindawi.com)
  • The dendritic cell-T-lymphocyte interaction is dependent on many stimulatory and co-stimulatory molecules to exert various physiological effect. (medscape.com)
  • However, secondary signal through co-stimulatory molecules is required to completely activate T-lymphocytes. (medscape.com)
  • Previously, we have demonstrated a role for T-bet, a T helper 1/CD8 + T cell transcription factor (TF), and FoxP3, a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown. (frontiersin.org)
  • It is also highly expressed by FoxP3-positive regulatory T lymphocytes. (miltenyibiotec.com)
  • We hypothesized that blocking antibodies specific for PD-1 would disrupt this negative regulatory pathway and would result in enhanced CAR T-cell effector function. (sarcomahelp.org)
  • High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. (cusabio.com)
  • XELJANZ should be given to lymphocyte counts at baseline and after 4-8 weeks of treatment and for our industry will be followed for three additional years to monitor antibody persistence. (micronus.xyz)
  • The earliest cell in B-lymphocyte lineage that produces Ig is the pre-B lymphocyte. (medscape.com)
  • Dothel G, Raschi E, Rimondini R, De Ponti F. Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology. (wjgnet.com)
  • Lymphocytes are a type of white blood cell. (clinicaltrials.gov)
  • We also observed an association between the CD8/regulatory T-cell ratio and tumor stage. (ersjournals.com)
  • Drugs that act by inhibiting regulatory T cell function might offer new and effective ways to control the disease. (sloankettering.edu)
  • Parasites remain in the liver for only a short duration and there may not be sufficient time to recruit lymphocytes from other organs 21 . (nature.com)
  • Our studies are defining how epigenetic , transcriptional and post-transcriptional mechanisms co-operate to control lymphocyte development and immunological memory. (babraham.ac.uk)
  • The Cold War: A New History cytokines display from popular and lovely to on-line and regulatory, but what remains them not appears their Purchase to have, protect, induce, Sign, choose, Join, and use findings. (michael-noeres.de)
  • Les IFNγ et les IL-10 étaient significativement élevés chez ceux qui présentaient une néphropathie diabétique (ND) et une maladie rénale en phase terminale (MRPT) par rapport aux témoins et aux patients diabétiques sans ND. (who.int)
  • Although growth factors can be administered to patients to increase circulating neutrophils, there is no effective method to stimulate CD8 lymphocyte production in humans, in vivo. (elsevier.com)
  • This interaction is further supported by CD3 on T-lymphocytes. (medscape.com)
  • The 2005 Annual Summary of Performance provides an outline of Health Canada 's pre-market regulatory review performance of therapeutic products intended for human use, including pharmaceuticals, biologics and medical devices 3 . (canada.ca)
  • Interferon regulatory factors (IRFs) are transcription factors that activate Type I interferons. (unl.edu)