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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
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.
A classification of lymphocytes based on structurally or functionally different populations of cells.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
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.
Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
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.
An encapsulated lymphatic organ through which venous blood filters.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
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.
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.
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.
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.
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.
Antibodies produced by a single clone of cells.
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 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.
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.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
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)
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.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
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.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
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.
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.
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.
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.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
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.
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
Established cell cultures that have the potential to propagate indefinitely.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
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.
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).
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.
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
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.
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.
Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.
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.
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.
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.
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.
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.
Conditions in which there is histological damage to the lower epidermis along with a grouped chronic inflammatory infiltrate in the papillary dermis disturbing the interface between the epidermis and dermis. LICHEN PLANUS is the prototype of all lichenoid eruptions. (From Rook et al., Textbook of Dermatology, 4th ed, p398)
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.
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.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
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 fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
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.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Sites on an antigen that interact with specific antibodies.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.
Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-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 group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.
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.
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.
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)
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
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.
A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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)
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
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.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.
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.
Glycoproteins found on the membrane or surface of cells.
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.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
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 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 subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
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).
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.
Substances that are recognized by the immune system and induce an immune reaction.
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.
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.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
The major group of transplantation antigens in the mouse.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a 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.
A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
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.
Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.
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.
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.
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)
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.
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.
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.
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.
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).
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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.
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.
An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.
Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.
A class of lymphocytes characterized by the lack of surface markers specific for either T or B lymphocytes.
Adherence of cells to surfaces or to other cells.
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 technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
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.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
Substances elaborated by viruses that have antigenic activity.
An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
Reduction in the number of lymphocytes.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.
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).
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
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.
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.
Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.
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.
Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.
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.
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.
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.
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.
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.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
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.
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.
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.
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 increased reactivity to specific antigens mediated not by antibodies but by cells.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.
Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.
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.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
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.
Progenitor cells from which all blood cells derive.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
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.
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.
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
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.

Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL). (1/13590)

Fas ligand is a type II transmembrane protein which can induce apoptosis in Fas-expressing cells. Recent reports indicate that expression of FasL in transplanted cells may cause graft rejection and, on the other hand, tumor cells may lose their tumorigenicity when they are engineered to express FasL. These effects could be related to recruitment of neutrophils by FasL with activation of their cytotoxic machinery. In this study we investigated the antitumor effect of allogenic fibroblasts engineered to express FasL. Fibroblasts engineered to express FasL (PA317/FasL) did not exert toxic effects on transformed liver cell line (BNL) or colon cancer cell line (CT26) in vitro, but they could abrogate their tumorigenicity in vivo. Histological examination of the site of implantation of BNL cells mixed with PA317/FasL revealed massive infiltration of polymorphonuclear neutrophils and mononuclear cells. A specific immune protective effect was observed in animals primed with a mixture of BNL or CT26 and PA317/FasL cells. Rechallenge with tumor cells 14 or 100 days after priming resulted in protection of 100 or 50% of animals, respectively. This protective effect was due to CD8+ cells since depletion of CD8+ led to tumor formation. In addition, treatment of pre-established BNL tumors with a subcutaneous injection of BNL and PA317/FasL cell mixture at a distant site caused significant inhibition of tumor growth. These data demonstrate that allogenic cells engineered with FasL are able to abolish tumor growth and induce specific protective immunity when they are mixed with neoplastic cells.  (+info)

Generation of CD8(+) T-cell responses to Mycobacterium bovis and mycobacterial antigen in experimental bovine tuberculosis. (2/13590)

Protective immunity against tuberculosis is considered to be essentially cell mediated, and an important role for CD8(+) T lymphocytes has been suggested by several studies of murine and human infections. The present work, using an experimental model of infection with Mycobacterium bovis in cattle, showed that live M. bovis elicits the activation of CD8(+) T cells in vitro. However, a sonic extract prepared from M. bovis (MBSE) and protein purified derivative (PPDb) also induced a considerable degree of activation of the CD8(+) T cells. Analysis of proliferative responses of peripheral blood mononuclear cells, purified CD8(+) T cells, and CD8(+) T-cell clones to M. bovis and to soluble antigenic preparations (MBSE, PPDb) showed that the responses of all three types of cells were always superior for live mycobacteria but that strong responses were also obtained with complex soluble preparations. Furthermore, while cytotoxic capabilities were not investigated, the CD8(+) T cells were found to produce and release gamma interferon in response to antigen (live and soluble), which indicated one possible protective mechanism for these cells in bovine tuberculosis. Finally, it was demonstrated by metabolic inhibition with brefeldin A and cytochalasin D at the clonal level that an endogenous pathway of antigen processing is required for presentation to bovine CD8(+) cells and that presentation is also dependent on phagocytosis of the antigen.  (+info)

Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T cells cause muscle cell injury directly in polymyositis. (3/13590)

OBJECTIVE: To investigate the involvement of the Fas/Fas ligand (Fas/FasL) system in the inflammatory myopathies. METHODS: Frozen muscle sections obtained from 7 patients with polymyositis (PM), 4 patients with dermatomyositis (DM), and 3 controls were studied by immunochemistry. Apoptosis was detected by DNA electrophoresis and in situ labeling using the TUNEL method. RESULTS: Fas was detected on muscle fibers and infiltrating mononuclear cells (MNC) in 6 PM patients and 2 DM patients. FasL was expressed mainly on CD4+ T cells and some CD8+ T cells, and on macrophages surrounding Fas-positive muscles in 4 PM patients and 1 DM patient. In 3 of the 5 patients with FasL-positive MNC, the TUNEL method showed that both invaded myonuclei and MNC underwent apoptosis. Chromosomal DNA from the muscle tissue of these patients showed ladder formation. CONCLUSION: Fas/FasL is involved in muscle cell apoptosis in at least 2 of the inflammatory myopathies, PM and DM. Although CD8+-mediated cytotoxicity is thought to be the main mechanism of muscle injury in PM, our data suggest that CD4+ T cells also directly cause muscle cell damage.  (+info)

Protection against lymphocytic choriomeningitis virus infection induced by a reduced peptide bond analogue of the H-2Db-restricted CD8(+) T cell epitope GP33. (4/13590)

Recent investigations have suggested that pseudopeptides containing modified peptide bonds might advantageously replace natural peptides in therapeutic strategies. We have generated eight reduced peptide bond Psi(CH2-NH) analogues corresponding to the H-2Db-restricted CD8(+) T cell epitope (called GP33) of the glycoprotein of the lymphocytic choriomeningitis virus. One of these pseudopeptides, containing a reduced peptide bond between residues 6 and 7 (Psi(6-7)), displayed very similar properties of binding to major histocompatibility complex (MHC) and recognition by T cell receptor transgenic T cells specific for GP33 when compared with the parent peptide. We assessed in vitro and in vivo the proteolytic resistance of GP33 and Psi(6-7) and analyzed its contribution to the priming properties of these peptides. The Psi(6-7) analogue exhibited a dramatically increased proteolytic resistance when compared with GP33, and we show for the first time that MHC-peptide complexes formed in vivo with a pseudopeptide display a sustained half-life compared with the complexes formed with the natural peptide. Furthermore, in contrast to immunizations with GP33, three injections of Psi(6-7) in saline induced significant antiviral protection in mice. The enhanced ability of Psi(6-7) to induce antiviral protection may result from the higher stability of the analogue and/or of the MHC-analogue complexes.  (+info)

Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells. (5/13590)

Inappropriate immune responses, thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology, could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigen-presenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore, we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS. These dendritic cells expressed numerous T-cell chemokines, but only in the presence of antigen did leukocytes accumulate in the ventricles, meninges, sub-arachnoid spaces, and injection site. Within the CNS parenchyma, the injected dendritic cells migrated preferentially into the white matter tracts, yet only a small percentage of the recruited leukocytes entered the CNS parenchyma, and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4+ T cells in the models used here, CD8+ T cells accumulated in numbers equal to or greater than that of CD4+ T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4), and those that did were primarily in the meninges, injection site, ventricles, and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen.  (+info)

N,N'-Diacetyl-L-cystine-the disulfide dimer of N-acetylcysteine-is a potent modulator of contact sensitivity/delayed type hypersensitivity reactions in rodents. (6/13590)

Oral N-acetyl-L-cysteine (NAC) is used clinically for treatment of chronic obstructive pulmonary disease. NAC is easily oxidized to its disulfide. We show here that N,N'-diacetyl-L-cystine (DiNAC) is a potent modulator of contact sensitivity (CS)/delayed type hypersensitivity (DTH) reactions in rodents. Oral treatment of BALB/c mice with 0.003 to 30 micromol/kg DiNAC leads to enhancement of a CS reaction to oxazolone; DiNAC is 100 to 1000 times more potent than NAC in this respect, indicating that it does not act as a prodrug of NAC. Structure-activity studies suggest that a stereochemically-defined disulfide element is needed for activity. The DiNAC-induced enhancement of the CS reaction is counteracted by simultaneous NAC-treatment; in contrast, the CS reaction is even more enhanced in animals treated with DiNAC together with the glutathione-depleting agent buthionine sulfoximine. These data suggest that DiNAC acts via redox processes. Immunohistochemically, ear specimens from oxazolone-sensitized and -challenged BALB/c mice treated with DiNAC display increased numbers of CD8(+) cells. DiNAC treatment augments the CS reaction also when fluorescein isothiocyanate is used as a sensitizer in BALB/c mice; this is a purported TH2 type of response. However, when dinitrofluorobenzene is used as a sensitizer, inducing a purported TH1 type of response, DiNAC treatment reduces the reaction. Treatment with DiNAC also reduces a DTH footpad-swelling reaction to methylated BSA. Collectively, these data indicate that DiNAC in vivo acts as a potent and effective immunomodulator that can either enhance or reduce the CS or DTH response depending on the experimental conditions.  (+info)

Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. (7/13590)

Dendritic cells (DC) are critically involved in the initiation of primary immune processes, including tumor rejection. In our study, we investigated the effect of interleukin-10 (IL-10)-treated human DC on the properties of CD8(+) T cells that are known to be essential for the destruction of tumor cells. We show that IL-10-pretreatment of DC not only reduces their allostimulatory capacity, but also induces a state of alloantigen-specific anergy in both primed and naive (CD45RA+) CD8(+) T cells. To investigate the influence of IL-10-treated DC on melanoma-associated antigen-specific T cells, we generated a tyrosinase-specific CD8(+) T-cell line by several rounds of stimulation with the specific antigen. After coculture with IL-10-treated DC, restimulation of the T-cell line with untreated, antigen-pulsed DC demonstrated peptide-specific anergy in the tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells reversed the state of both alloantigen- or peptide-specific anergy. In contrast to optimally stimulated CD8(+) T cells, anergic tyrosinase-specific CD8(+) T cells, after coculture with peptide-pulsed IL-10-treated DC, failed to lyse an HLA-A2-positive and tyrosinase-expressing melanoma cell line. Thus, our data demonstrate that IL-10-treated DC induce an antigen-specific anergy in cytotoxic CD8(+) T cells, a process that might be a mechanism of tumors to inhibit immune surveillance by converting DC into tolerogenic antigen-presenting cells.  (+info)

Phenotypic and functional characterization of CD8(+) T cell clones specific for a mouse cytomegalovirus epitope. (8/13590)

A series of CD8(+) T cell clones, specific for the IE1 epitope YPHFMPTNL, of the immediate-early protein 1 of the murine cytomegalovirus (MCMV) were generated in order to determine their protective activity against this infection and correlate their phenotypic markers with antiviral activity. We found that the adoptive transfer of three of these anti-MCMV CD8(+) T cell clones into irradiated naive mice resulted in protection against challenge, while another CD8(+) T cell clone, of the same specificity, failed to confer protection. The clones that conferred protection against lethal challenge reduced greatly viral replication in the lung and other organs of the mice. Using one of the protective anti-MCMV CD8(+) T cell clones we found that in order to be fully protective the cells had to be transferred to recipient mice no later than 1 day after MCMV challenge. The adoptive transfer of these CD8(+) T cell clones also protected CD4(+) T-cell-depleted mice. Phenotypic characterization of the anti-MCMV clones revealed that the nonprotective clone expressed very low levels of CD8 molecules and produced only small amounts of TNF-alpha upon antigenic stimulation. Most importantly, our current study demonstrates that this MHC class I-restricted IE1 epitope of MCMV is efficiently presented to CD8(+) T cell clones in vivo and further strengthens the possibility of the potential use of CD8(+) T cell clones as immunotherapeutic tools against cytomegalovirus-induced disease.  (+info)

Persistent human papillomavirus (HPV) type 16 and 18 infection can lead to pre-malignant and malignant diseases of the lower genital tract. Several lines of evidence suggest that T cell responses can control HPV infection. However, relative to other human viruses, strong effector memory T cell responses against HPV have been difficult to detect. We used an in vitro stimulation step prior to enzyme-linked immunospot assays to identify IFN-gamma-secreting T cells specific for HPV16 and 18 E6/E7 peptides. This allowed the detection of HPV-specific CD4+ T cells that were not evident in direct ex vivo assays. T cell responses against HPV16 or 18 peptides were detected in healthy volunteers (7/9) and patients with lower genital tract neoplasia (10/20). Importantly, this assay allowed tracking of vaccine-induced T cell responses in nine patients, following inoculation with a live recombinant vaccinia virus (HPV16 and 18 E6/E7, TA-HPV). Novel vaccine-induced T cell responses were demonstrated in five ...
The results presented herein suggest that generation of an effective influenza-specific CD8 T cell response requires activated CD8 T cells to interact with pulmonary pDCs, CD8α+ DCs, or iDCs in a MHC class I-, viral epitope-dependent manner once they enter the lungs. This secondary interaction is in addition to the initial DC-T cell interactions that occur in the LN during activation of naive CD8 T cells. To our knowledge, this is the first study detailing a critical role for peripheral DC-CD8 T cell interactions after initial programming of primary effector T cells in the LN. This suggests that the influenza-specific CD8 T cell response may be regulated by a two-hit model of development and that the magnitude, and possibly phenotype, of the peripheral CD8 T cells generated may be related to both the initial programming that occurs in the LN, but also by secondary contacts with DC subsets at the site of the infection. Of note, we have observed differential magnitudes of recruitment into the ...
p286/I-Ag7 tetramer-positive CD4+ T cells from G286 mice delay diabetes transfer. Tetramer-positive and -negative cells were sorted from G286 lymph node cells w
We show here that HCV-specific CD8+ T cells can be frequently detected in HCV-seronegative (HCV-SN) individuals and that these cells may impact the response to vaccination. Virus-specific T cell responses in unexposed individuals have been reported before in several settings (15, 16, 19, 32), and the composition of this preexisting T cell repertoire may influence the response toward vaccines, as suggested by reports for other infections (14, 33). However, thus far, no study has systematically studied the frequency and repertoire of HCV-specific CD8+ T cell responses in a large number of HCV-SN individuals and investigated how preexisting HCV-specific CD8+ T cells may influence vaccine responses. Our study, which included a total of 121 HCV-SNs, revealed a high prevalence of HCV NS3-1073-specific CD8+ T cell responses both ex vivo, as well as in vitro in about one-third of individuals tested, whereas the NS3-1073-specific T cell responses were low or absent in the remaining two-thirds. However, ...
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccines protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine. A robust antibody response in all of the donors after vaccination was observed. Though no CD8(+) T-cell responses to known epitopes were detected, HA-specific T-cell responses were primed following vaccination, and the responses were found to be mainly CD4(+) T-cell dependent. However, ...
T cell responses play an important role in the outcome of HBV and HCV infection, e.g. viral elimination versus persistence. However, multiple mechanisms can lead to the failure of the virus-specific T cell response. These mechanisms include primary T cell failure, T cell exhaustion, the emergence of viral escape mutants, as well as T cell dysfunction. Furthermore, genetic factors such as the individual HLA allele background play an important role in the outcome of infection. Once viral persistence has been established, HBV or HCV infection can progress to liver fibrosis and cirrhosis with an enhanced risk for HCC. Tumor-specific T cells (e.g. AFP-specific T cells) are thought to contribute to cancer control.. The focus of our group is the identification and characterization of virus-specific CD4+ and CD8+ T cell responses during acute and chronic HBV and HCV infection with a special focus on intrahepatic T cell responses as well as the mechanisms of viral persistence (e.g., viral escape, T cell ...
The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface. Liposomal vaccine particles were engineered to display the malaria circumsporozoite (CSP) antigen on their surface, with helper CD4+ epitopes from distinct vaccine or viral antigens contained within the particle core, ensuring the B cell response is raised but focused against CSP. In vivo vaccination studies were then conducted in C57Bl/6 mice as models of either vaccine-induced pre-existing CD4+ T cell immunity (using ovalbumin-OVA)
Autoreactive CD8 T cells play a central role in the destruction of pancreatic islet β-cells that leads to type 1 diabetes, yet the key features of this immune-mediated process remain poorly defined. In this study, we combined high-definition polychromatic flow cytometry with ultrasensitive peptide-human leukocyte antigen class I tetramer staining to quantify and characterize β-cell-specific CD8 T cell populations in patients with recent-onset type 1 diabetes and healthy control subjects. Remarkably, we found that β-cell-specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy control subjects, however, patients with newly diagnosed type 1 diabetes displayed hallmarks of antigen-driven expansion uniquely within the β-cell-specific CD8 T cell compartment. Molecular analysis of selected β-cell-specific CD8 T cell populations further revealed highly skewed oligoclonal T cell receptor repertoires comprising exclusively private clonotypes. ...
Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central ...
T cell exhaustion is a major factor in failed pathogen clearance during chronic viral infections. Immunoregulatory pathways, such as PD-1 and IL-10, are upregulated upon this ongoing antigen exposure and contribute to loss of proliferation, reduced cytolytic function, and impaired cytokine production by CD4 and CD8 T cells. In the murine model of LCMV infection, administration of blocking antibodies against these two pathways augmented T cell responses. However, there is currently no in vitro assay to measure the impact of such blockade on cytokine secretion in cells from human samples. Our protocol and experimental approach enable us to accurately and efficiently quantify the restoration of cytokine production by HIV-specific CD4 T cells from HIV infected subjects. Here, we depict an in vitro experimental design that enables measurements of cytokine secretion by HIV-specific CD4 T cells and their impact on other cell subsets. CD8 T cells were depleted from whole blood and remaining PBMCs were ...
Improving adaptive anti-viral responses: a key to eliminating persistent viral infection. HCMV establishes a persistent infection, and although in a healthy subject infection is generally asymptomatic, infection of immunocompromised hosts leads to severe disease. Using the MCMV-infection model, recent studies have shown that MCMV-susceptible and MCMV-resistant mouse strains have functional differences in the efficacy of the antiviral CD4+ and CD8+ T cell responses and in the ability to control persistent virus. These studies provided evidence to indicate that antiviral T cell responses are negatively affected by natural killer (NK) cells. Our data indicate that the NK cell-mediated elimination of virus-infected dendritic cells (DC) may be the key event in this process. Ongoing studies will address how T cells control persistent infection and how their anti-viral activity can be restored therapeutically. This research will help us understand viral pathogenesis and importantly will provide ...
This thesis focuses on the decision making in the most common business form: family businesses. A well-established theoretical model within the family business field is The three circle-model, which is based on three different dimensions: family, ownership and business. Most of the family businesses stay small but the ones expanding face the dilemma of balancing the best development of the dimensions. However, these three dimensions can contradict each other and as a result the founders are forced to choose which of the dimensions to prioritize when taking decisions.The purpose of this thesis is to create an understanding of how the family, the ownership and the business dimensions affect founders thoughts and reasoning behind decisions in the expansion phase in first generation family firms with few owners.We have reached the conclusions with a qualitative approach using case studies. We have gathered the empirical data by using Life story and Critical incident to define expansion decisions in ...
Sergeev, V.A. and Kubyshkina, M.V. and Baumjohann, W. and Nakamura, R. and Amm, O. and Pulkkinen, T. and Angelopoulos, V. and Mende, S.B. and Klecker, B. and Nagai, T. and Sauvaud, J.-A. and Slavin, J.A. and Thomsen, M.F. (2005) Transition from substorm growth to substorm expansion phase as observed with a radial configuration of ISTP and Cluster spacecraft. Annales Geophysicae, 23 (6). pp. 2183-2198. ISSN 0992-7689 ...
Gras, S. et al. (2010). Allelic polymorphism in the T cell receptor and its impact on immune responses. Journal of Experimental Medicine. 207(7): 1555-67. [PubMed ID 20566715]. Though many millions of T cell receptor (TCR) specificities are possible, there are often strong population biases in the presence of particular TCRs specific for disease epitopes. Using ProImmune Pro5® MHC Class I Pentamers, Gras et al. addressed the previously overlooked question of the impact of sequence variation in the TCR on immunity. They demonstrated that a single amino acid difference within a TCR can reduce its binding affinity for a viral peptide-MHC complex and preclude its dominance in an antiviral T cell response.. As their model system, the team chose to employ the HLA-B*35:01 - restricted HPVGEADYFEY (HPVG) epitope from the EBNA-1 protein of Epstein Barr Virus (EBV), which is highly immunogenic in EBV-exposed individuals. They established that the T cell response to this epitope is characterized by biases ...
Abstract In a human melanoma model of tumor antigen (TA)-based immunization, we tested the functional status of TA-specific CD8+ cytotoxic T lymphocytes. A quiescent phenotype lacking direct ex vivo cytotoxic and proliferative potential was identified that was further characterized by comparing its transcriptional profile to that of TA-specific T cells sensitized in vitro by exposure to the same TA and the T-cell growth factor interleukin 2 (IL-2). Quiescent circulating tumor-specific CD8+ T cells were deficient in expression of genes associated with T-cell activation, proliferation, and effector function. This quiescent status may explain the observed lack of correlation between the presence of circulating immunization-induced lymphocytes and tumor regression. In addition, the activation of TA-specific T cells by in vitro antigen recall and IL-2 suggests that a complete effector phenotype might be reinstated in vivo to fulfill the potential of anticancer vaccine protocols.. ...
T cells play pivotal roles in shaping host immune responses in infectious diseases, autoimmunity and cancer. The activation of T cells requires immune and growth factor-derived signals. However, alterations in nutrients and metabolic signals tune T cell responses by impinging upon T cell fates and immune functions. In this review, we summarize how key nutrients, including glucose, amino acids and lipids, and their sensors and transporters shape T cell responses. We also briefly discuss regulation of T cell responses by oxygen and energy sensing mechanisms.
As the central player in the immune response fighting against pathogen invasions in mammals, the activation of T cells must be tightly regulated. Proper resolution of a T cell response is as essential as its initiation because of the possible severe pathological consequences of a hyperinflammatory response. NF-κB activation is a key signaling event downstream of TCR engagement and regulates almost all of the important aspects of T cell activation. Because of its pivotal role, NF-κB activation in T cells is regulated through a multilayered negative regulatory network (Schulze-Luehrmann and Ghosh, 2006). In this study, we identified miR-146a as an important new member of the negative feedback loop that modulates TCR signaling to NF-κB and demonstrated its physiological role in regulating both acute T cell response and chronic hyperinflammatory autoimmune T cell response in vivo. Based on these results, we propose a model of miR-146a as an important new constituent of the negative feedback ...
The drug being tested in this study is called TAK-169. The study will evaluate the safety, tolerability, preliminary efficacy, PK, pharmacodynamic, and immunogenicity of TAK-169 monotherapy in participants with RRMM.. The study will be conducted in 2 phases: Dose Escalation Phase (Part 1) and an Expansion Phase (Part 2). The study will enroll approximately 81 to 102 participants (39 to 60 participants in Part 1 and approximately 54 participants in Part 2).. In the Dose Escalation Phase (Part 1), the starting dose level will be 50 microgram/kilogram (mcg/kg), once weekly. On the basis of investigator and sponsor review of available safety, PK, pharmacodynamic, and efficacy data from Cohort 1, the dose will be escalated in the subsequent cohorts to 100, 200, 335, 500, and 665 mcg/kg, once weekly. A separate dose escalation may also occur in which TAK-169 will be administered once every 2 weeks.. In the Expansion Phase (Part 2), the study will evaluate two types of RRMM cohorts: ...
Spleen 3 days after immunisation. B cells (red), CTL (green) and dendritic cells (blue I noted some time ago that, despite the name, its clear that cytotoxic T
The scope of the genital herpes problem is daunting. The disease-technically known as HSV-2-affects one in every six people between the ages of 14 and 49 in the United States. Worldwide infection estimates reach 500 million. An approved vaccine would have the potential to impact patients on so many levels, says Darren Higgins, co-founder of…
These kits utilize a patented technique for exchanging up to ten peptides on an MHC class I tetramer. Components for quantifying the extent of peptide exchange by flow cytometry are included ...
Researchers have discovered that an important part of the immune system puts up a strong anti-inflammatory T cell response following the development of atherosclerotic lesions.
A major challenge in the HIV field has been to understand why the strength of virus-specific CD8 T cell responses has no relationship to viral load, and yet CD8 depletion studies indicate that these cells are critical for immune control. And a major challenge in the field of immunology in general has been the rapid translation of advances in murine models to humans. In late 2005, through a telephone conversation with Rafi Ahmed, we became aware of yet unpublished data in the mouse model of chronic infection. His laboratory had shown that in mice persistently infected with LCMV, T cells up-regulate a surface molecule termed PD-1, for programmed death-1, a negative immunoregulatory molecule that turned off CD8 T cell function. The potential parallels with HIV were immediately obvious to us-perhaps persistent exposure to HIV was having a similar impact on CD8 T cell function in humans, and perhaps similar immune regulation was rendering CD4 T cells exhausted as well.. We immediately formed a ...
The contraction phase of T cell activation is an important part of the immune response. A recent paper looks at the mechanisms involved
bricko sends this disappointing but not unexpected news from Techdirt: While it didnt get nearly as much attention as other parts of SOPA, one section in the bill that greatly concerned us was the massive expansion of the diplomatic corp.s IP attaches. If youre unfamiliar with the program, bas...
While MHC class Ia-restricted CD8 T cell responses to viral infections have been extensively characterized, little is known about MHC class Ib-restricted CD8 T cells during viral infection. Mouse polyoma virus establishes a persistent low-level infection and induces tumors in MHC class Ia + class Ib deficient (i.e., b2m−/−) mice. Unexpectedly, mice selectively deficient for MHC class Ia molecules (i.e., Kb−/−Db−/−) mice efficiently control polyoma viral replication and are resistant to polyoma virus-induced tumors. Polyoma virus-specific CD8 T cell cloned lines were isolated from immune Kb−/−Db−/− mice. Using these cloned lines, we mapped their MHC restriction to H2-Q9, an MHC Class Ib molecule of the Qa-2 family. We identified the Q9-restricted viral epitope as a 9mer peptide from a viral capsid protein. In preliminary studies, we found that the magnitude of the Q9-restricted antiviral CD8 T cell response progressively inflates over the course of infection. Experiments are ...
Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombinant bovine β2-microglobulin from which p-MHC class I tetramers can be derived in ~48 h. We validated a set of p-MHC class I tetramers against a panel of CTL lines specific to seven epitopes on five different antigens of Theileria parva, a protozoan pathogen causing the lethal bovine disease East Coast fever. One of the p-MHC class I tetramers was tested in ex vivo assays and we detected T. parva specific CTL in peripheral blood of cattle at day 15-17 post-immunization with a live parasite vaccine. The algorithm NetMHCpan predicted alternative epitope sequences for some of the T. parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new ...
The primary goal of this study was to resolve the uncertainty about whether HESNs make T cell responses to HIV-1. We compared the frequencies of HIV-1-specific T cell responses over time between HESN and HUSN groups in a powered, blind study with independent data analysis. In these donors, no T cell responses were detectable without culture, except, notably, in an HESN participant who was homozygous for CCR5Δ32 and therefore genetically resistant to HIV-1 infection (18, 46). Using the more sensitive cultured ELISpot assay, T cell responses were found in both HESNs and HUSNs. Significant differences were found in the frequencies of T cell responses over time, with HESNs more likely to have positive T cell responses than HUSNs. HESNs more often maintained HIV-1-specific T cell responses across visits than HUSNs. Also, among positive responders, T cell responses were of significantly higher magnitude in HESNs than in HUSNs. Given that the cultured ELISpot assay expands antigen-specific cells ...
How vaccines control the development of antigen-specific effector and memory T helper cells is central to protective immunity but remains poorly understood. Here we found that protein vaccination selected high-affinity, CXCR5+ICOS(hi) follicular B-helper T cells (T(FH) cells) that developed in draining lymphoid tissue to regulate B cell responses. In the memory phase, reservoirs of antigen-specific CXCR5+ICOS(lo) T(FH) cells persisted with less effector activity but accelerated antigen-recall ability. This new compartment of memory T(FH) cells was retained in draining lymphoid sites with antigen-specific memory B cells, persistent complexes of peptide and major histocompatibility complex class II and continued expression of CD69. Thus, protein vaccination promotes B cell immunity by selecting high-affinity effector T(FH) cells and creating lymphoid reservoirs of antigen-specific memory T(FH) cells in vivo ...
T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our ...
What are the decisive factors that determine which effector cells survive to become long-lived memory cells and which cells die during the contraction phase? We have characterized the transcriptome of effector and memory T cells and identified genetic pathways and several transcription factors that regulate this life or death decision in activated T cells. Our work has helped to outline a model of effector T cell differentiation wherein a small subset of T cells develop into memory precursor cells that are more fit to persist following the first infection than the majority of effector cells. These memory precursor cells develop into long-lived memory T cells that protect against re-infection. Several types of memory T cells, which differ by their phenotypes, functions and anatomical locations, are produced to create a sophisticated, multi-layered defense system. Conceptually, the memory T cells are divided into three subsets: (1) Tissue resident memory T (TRM) cells, which locally reside in ...
The original study of EBV-specific CD8+ responses with HLA class I tetramers was the first to show definitively that Ag-experienced CD8+ T cells in man could be phenotypically heterogeneous in terms of CD45RO vs RA expression and in terms of CD28 status (3). The present work was prompted by our observation that these tetramer-staining CD8+ populations also appeared functionally heterogeneous, in that only 20-40% of tetramer-positive cell numbers were detected in ELISPOT assays of peptide-induced IFN-γ release (21). Our aim was to readdress the much discussed relationship between CD8+ T cell phenotype, type I cytokine production, and cytotoxic capacity (7, 8, 10, 11, 12, 31) with assays specific for the cognate epitope rather than the nonspecific assays (PMA/ionomycin stimulation and anti-CD3 redirected cytotoxicity respectively) that had been used to date. As others have reported (22, 33), we found that staining for the tetramer, CD8, and a third surface marker of choice could be combined with ...
BACKGROUND: The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined. METHODS: HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence. RESULTS: The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus-specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non
T cells are critical to generate early control and clearance of many viral infections of the respiratory system (3). Recent studies in transgenic mouse models provided evidence that T cells are also important for viral clearance and disease resolution after SARS-CoV-2 infection (4). Hence, it is expected that T cell activation has emerged as a hallmark of acute COVID-19, probably as a consequence of an early SARS-CoV-2-specific cellular immune response (5-9). Although early T cell responses may play a critical role in dampening disease severity, there are also reports describing a dysregulated and unchecked T cell activation pattern in severe cases (10-12). Increased T cell activation in severe cases likely reflects increased antigen levels in the respiratory system, but whether the early T cell response reaches a state of exhaustion in individuals with severe hyperinflammation remains to be determined. Furthermore, given that COVID-19 is a disease of the respiratory tract, it will be important ...
TY - JOUR. T1 - Differentiation of CD8 T cells in response to acute and chronic viral infections. T2 - Implications for HIV vaccine development. AU - Miller, J. D.. AU - Masopust, D.. AU - Wherry, E. J.. AU - Kaech, S.. AU - Silvestri, G.. AU - Ahmed, R.. PY - 2005/6/1. Y1 - 2005/6/1. N2 - Successful HIV vaccine strategies will likely require the induction of robust cellular immune responses, in addition to strong humoral responses. Unfortunately, there is no clear molecular definition of an effective HIV-specific CD8 T cell response. In this review, we discuss the differentiation of CD8 T cells in response to acute and chronic viral infections. We then apply concepts derived from these studies to predict the desirable characteristics of HIV-specific CD8 T cell memory.. AB - Successful HIV vaccine strategies will likely require the induction of robust cellular immune responses, in addition to strong humoral responses. Unfortunately, there is no clear molecular definition of an effective ...
The specificity of T cells is determined by the TCR. T cell populations activated and expanded during most in vivo antigen challenges are highly complex, with diverse TCR repertoires, complicating the detection of these cells. The ideal reagent to identify complex epitope-specific T cell populations would be the natural ligand of the TCR, the MHC/epitope complex. However, the affinity of the TCR-MHC/epitope interaction is very low; the association is characterized by a particularly high dissociation rate. To increase the overall avidity of this interaction, MHC/epitope complexes are multimerized into e.g. tetramers. MHC tetramer reagents conjugated with a fluorescent dye can be used in flow cytometry, allowing highly specific detection and isolation of (complex) epitope specific T cell populations directly ex vivo.. The generation of MHC class I multimer reagents has become well established over the past few years. Beta-2-microglobulin and the heavy chains (HC) of MHC molecules are expressed as ...
Purpose: NY-ESO-1 (ESO), a tumor specific antigen of the Cancer/Testis group, is presently viewed as an important model antigen for the development of generic anti-cancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we have generate DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T cell responses in vaccinated patients expressing DR1. Experimental design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143 specific CD4 T cells in peptide-stimulated post-vaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer+ cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4+ DR1/ESO119-143 tetramer+ T cells ex vivo and characterized them phenotypically. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. Tetramer+ cells ...
Purpose: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1).. Experimental Design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143-specific CD4 T cells in peptide-stimulated postvaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer+ cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4+ DR1/ESO119-143 tetramer+ T cells ex vivo and characterized them phenotypically.. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. ...
The adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) or TCR-redirected peripheral blood lymphocytes (PBL) is a promising treatment for patients with metastatic cancer (48, 49). The experiments described in this report show that small numbers of tumor antigen-specific CD8+ T cells engineered to produce high levels of IL-12 can lead to the regression of large vascularized tumors without the need for exogenous IL-2 or vaccine in lymphodepleted hosts. The marked improvement in treatment was associated with an increase in tumor infiltration by adoptively transferred T cells, along with an increase in endogenous NK cells and endogenous CD8+ T cells from the reconstituting host. Based on the delayed kinetics of tumor destruction, modulation of endogenous host immune cells likely plays an important role in facilitating tumor destruction, but the effect of host NK cells and CD8+ T cells remains unclear.. Nevertheless, one of our key findings in this study included isolating ...
Mono-7D6-Fab co-potentiated TCR/CD3 signaling in response to weak pMHC antigens that possessed a critical minimal antigenic strength. Here, we present the main model of receptor co-potentiation by an otherwise intrinsically inert monovalent Fab (fig. S8). Ligation of TCR/CD3 by weak antigens induces weak signal transduction and weak T cell responses (fig. S8A). In contrast, ligation by anti-TCR/CD3 monovalent Fab is inert, inducing no classical signal transduction and producing no functional T cell response even though such Fab binding may induce biophysical alteration to the receptor (fig. S8B). The co-potentiation principle states that weak antigenic ligation plus intrinsically inert monovalent Fab ligation can synergize to enhance TCR signaling and T cell responses (fig. S8C).. The identification of specific properties displayed by Mono-7D6-Fab permitted an investigation of the co-potentiation concept. Mono-7D6-Fab did not impede pMHC:TCR interactions and did not intrinsically induce TCR/CD3 ...
Due to an increase in its expression following the activation of B-cells and T-cells, CD44 can serve as a valuable marker for memory cells. Furthermore, the upregulation of CD44 expression is sustained on effector cells and memory cells after the immune response has subsided, so CD44 expression can also be used as an indicator of prior exposure to an antigen. However, little is currently known about its function of T cells. Recent studies have suggested that the CD44 signaling pathway may be involved in ensuring proper T cell effector responses by providing contextual signals at various anatomical sites. CD44 ligation may also promote T cell survival through the augmentation of T cell activation in response to an antigen. Studies also suggest that CD44 may contribute to both the regulation of the contraction phase of an immune response and the maintenance of immune tolerance. Furthermore, CD44 may play a role in ensuring the functional fitness of memory T cells once the memory stage has been ...
of research plan for MERIT extension. Memory T cell populations with a history of repeated antigen exposure will be generated in humans due to recurring infecti...
JPT Peptide Technologies is a DIN ISO 9001:2015 certified and GCLP compliant integrated provider of innovative peptide based catalog products and custom services.
Inflammatory reactions are believed to be triggered by innate signals and have a major protective role by recruiting innate immunity cells, favoring lymphocyte activation and differentiation, and thus contributing to the sequestration and elimination of the injurious stimuli. Although certain lymphocyte types such as TH17 cells co-participate in inflammatory reactions, their generation from the naïve pool requires the pre-existence of an inflammatory milieu. In this context, inflammation is always regarded as beginning with an innate response that may be eventually perpetuated and amplified by certain lymphocyte types. In contrast, we here show that even in sterile immunizations or in MyD88 deficient mice, CD8 T cells produce a burst of pro-inflammatory cytokines and chemokines. These functions follow opposite rules to the classic CD8 effector functions since they are generated prior to cell expansion and decline before antigen elimination. As few as 56 CD8+ inflammatory effector cells in a lymph node
A novel clinical-grade CD40L reagent was developed to test the hypothesis that immunization with functionally mature IL-12p70-producing DCs elicits effective CD8+ T immunity in patients with newly diagnosed advanced melanoma. Immunological responses to the gp100 antigen were observed in 6 of the 7 treated patients, while clinical response (as defined by RECIST criteria) was observed in 3 of 7 patients. Importantly, IL-12p70 levels produced by patient-derived CD40L/IFN-γ-activated mDCs as well as the development of antitumor Tc1 CD8+ T cell immunity correlated with TTP. Impairment in IL-12p70 production by CD40L/IFN-γ activated mDCs was observed in the 4 clinical nonresponder patients (all with Tc2-skewed immunity), and this deficiency resulted from impaired IL-12p35 subunit transcription. However, incorporating TLR3 and TLR8 signals with CD40L/IFN-γ activation corrected the IL-12p70 production defect in clinical nonresponder patient DCs, suggesting new ways to improve vaccine efficacy in ...
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Irreversible T cell exhaustion limits the efficacy of programmed cell death 1 (PD-1) blockade. We observed that dual CD40-TLR4 stimulation within a single tumor restored PD-1 sensitivity and that this regimen triggered a systemic tumor-specific CD8+ T cell response. This approach effectively treated established tumors in diverse syngeneic cancer models, and the systemic effect was dependent on the injected tumor, indicating that treated tumors were converted into necessary components of this therapy. Strikingly, this approach was associated with the absence of exhausted PD-1hi T cells in treated and distant tumors, while sparing the intervening draining lymph node and spleen. Furthermore, patients with transcription changes like those induced by this therapy experienced improved progression-free survival with anti-PD-1 treatment. Dual CD40-TLR4 activation within a single tumor is thus an approach for overcoming resistance to PD-1 blockade that is unique in its ability to cause the loss of ...
We used flow cytometry to investigate the percentage of IL-17-expressing blood T cells ex vivo in 49 healthy controls. Nonadherent PBMCs were stained for CD3, CD4, CD8, and IL-17. No IL-17-producing T cells were detected in the absence of activation (unpublished data). Upon activation with PMA-ionomycin, the percentage of CD3-positive cells producing IL-17 ranged from 0.06 to 2% (Fig. 1, A and B). The vast majority (,90%) of IL-17-positive cells were CD4-positive and CD8-negative (unpublished data). Thus, within the general population, there is considerable interindividual variability in the numbers of IL-17-producing cells present among freshly isolated T cells activated ex vivo. This makes it difficult to assess the impact of genetic lesions on the development of IL-17-producing T cells. We tested nine patients with null mutations in IRAK4 or MYD88, whose cells were unresponsive to IL-1β (and most TLRs and other IL-1 cytokine family members). The proportion of IL-17-producing T cells was not ...
Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and …
CD4+ T cells play a major role in adaptive immune responses to intracellular and extracellular microbes by regulating the functions of B cells, CD8+ T cells, an...
In order to more effectively address the expansion of type 2 diabetes worldwide, this study investigated the role that stressors and the stress response play in the development of diabetes. This study analyzed clinical ...
It remains difficult to treat the multiplicity of distinct viral infections that afflict immunocompromised patients. Adoptive transfer of virus-specific T cells (VSTs) can be safe and effective, but such cells have been complex to prepare and limited in antiviral range. We now demonstrate the feasib …
MHC Tetramers for detecting specific T-cell populations. Easy immuophenotyping of your t-cell sample! Class I and II antigen specific tetramers available.
Oxford Immunotec releases the T-SPOT Discovery SARS-CoV-2 kit for research into measuring the T cell immune response to SARS-CoV-2, which may offer new insights into immunity to COVID-19 ...
Many T lymphocytes were identified by these authors positive to CD4 and CD8. Macrophages and T lymphocytes demonstrated a ... The foam cells of monocyte/macrophage origin are positive for KP1, HAM56, CD11b and CD68 as pointed out by Nakashiro et al. in ... Under microscope, the cellular infiltrate includes neutrophils, lymphocytes, plasma cells, erythrocytes, hemosiderin-laden ...
The most activity was observed during the subacute phase with an increase in CD8 and CD4 lymphocytes. At this phase, clusters ... During the chronic phase, a high amount of CD4 T- cells and a few IgM-positive B-cells were observed. Immunosuppression ... Within the synovium collected, plasma cells and T-lymphocytes were the primary inflammatory cells present. During the acute- ... and T and B-lymphocytes were observed to determine its effects on cellular infiltrates during the development of reovirus ...
This infiltrate consists mainly of CD4 positive T lymphocytes with less CD8 positive lymphocytes and macrophages. Infiltration ... All these genes or their products more precisely are involved in T lymphocytes development. Derm1 region is conserved on human ...
... positive for both CD4 and CD8). The final stage in maturation is the single positive stage (positive for either CD4 or CD8). In ... Thymopoiesis is the process in the thymus by which thymocytes differentiate into mature T lymphocytes. The primary function of ... At this stage thymocytes upregulate both CD4 and CD8, becoming double positive cells. Double positive thymocytes that have a T ... Expression of both CD4 and CD8 makes them double positive, and matures into either CD4+ or CD8+ cells. Thymocytes are ...
Homozygous mutant animals had abnormal peripheral blood lymphocytes, specifically decreased CD8-positive T cell and NK cell ... numbers and an increase in CD4-positive T cells. The mice also had an abnormal integument phenotype determined by a study of ...
... cd8-positive t-lymphocytes MeSH A11.118.637.555.567.569.220.200 - t-lymphocytes, cytotoxic MeSH A11.118.637.555.567.569.500 - t ... cd4-positive t-lymphocytes MeSH A11.118.637.555.567.569.200.400 - t-lymphocytes, helper-inducer MeSH A11.118.637.555.567.569. ... b-lymphocyte subsets MeSH A11.118.637.555.567.550.500 - t-lymphocyte subsets MeSH A11.118.637.555.567.562 - b-lymphocytes MeSH ... lymphocyte subsets MeSH A11.118.637.555.567.622 - lymphocytes, null MeSH A11.118.637.555.567.650 - lymphocytes, tumor- ...
... cd8-positive t-lymphocytes MeSH A15.145.229.637.555.567.569.220.200 --- t-lymphocytes, cytotoxic MeSH A15.145.229.637.555.567. ... t-lymphocytes, regulatory MeSH A15.382.490.555.567.569.220 --- cd8-positive t-lymphocytes MeSH A15.382.490.555.567.569.220.200 ... cd4-positive t-lymphocytes MeSH A15.382.490.555.567.569.200.400 --- t-lymphocytes, helper-inducer MeSH A15.382.490.555.567.569. ... t-lymphocytes MeSH A15.145.229.637.555.567.569.200 --- cd4-positive t-lymphocytes MeSH A15.145.229.637.555.567.569.200.400 --- ...
... or CD8-positive lymphocytes and IgG4-positive plasma cells, and exhibits interstitial fibrosis and acinar cell atrophy in later ... It has been proposed that a cytologic smear primarily composed of acini rich in chronic inflammatory cells (lymphocytes, plasma ... Histopathologic examination of the pancreas shows fibrotic changes with lymphocyte and plasma cell infiltrate. For diagnosis, ...
CD8 ratio) is a basic laboratory test in which the percentage of CD3-positive lymphocytes in the blood positive for CD4 (T ... production of HIV specific CD8 positive cells will cause a large fall in the ratio, but subsequent immunosuppression over time ... Normal values (95% confidence intervals) are approximately 30-60% CD4 and 10-30% CD8 depending on age (ratio 0.9 to 3.7 in ... The T-Lymphocyte Helper/Suppressor Profile (Helper/Suppressor ratio, T4:T8 ratio, CD4: ...
T-PLL has the immunophenotype of a mature (post-thymic) T-lymphocyte, and the neoplastic cells are typically positive for pan-T ... The immunophenotype CD4+/CD8- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ ... A high lymphocyte count (> 100 x 109/L) along with low amounts of red blood cells and platelets in the blood are common ... In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilic cytoplasm with ...
... also called CD8 positive- or cytotoxic T-cells) that destroy cells. MHC class I proteins associate with β2-microglobulin, which ... HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. ... A representative cellular assay is the mixed lymphocyte culture (MLC) and used to determine the HLA class II types. The ... These particular antigens stimulate the multiplication of T-helper cells (also called CD4 positive T cells), which in turn ...
... for ALPS Mild elevations also found in other autoimmune diseases Thought to be cytotoxic T lymphocytes that have lost CD8 ... Can have antibodies to blood cells (DAT, anti-neutrophil, anti-platelet). Also, can have positive ANA, RF, ANCA Defective in ... It affects lymphocyte apoptosis. It is a RASopathy. It is a rare genetic disorder of abnormal lymphocyte survival caused by ... Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune ...
"Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder". ... Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive. Clonal rearrangements of the T-cell receptor ( ... are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T- ... The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in ...
CD7 positive T cells, CD3 negative, CD4 positive T cells, or CD3 positive, CD4 negative, CD8 negative T cells) and is thought ... In on study of 16 lymphocyte-variant hypereosinophilia patients with the aberrant CD3 negative, CD41 positive immunophenotype, ... in T-cells or the proliferation of lymphocytes with the CD3 negative, CD41 positive immunophenotype may occur during the ... Lymphocyte-variant hypereosinophilia is a disorder attributed to the expansion of a cytokine-producing, aberrant population of ...
... and different lymphocyte subtypes, reacting to CD3, CD4, CD8, CD20 and CD138. The sensitivity of McDonald criteria is low with ... In order to reduce false positives, McDonald et al. propose that their criteria should be applied only after any other disease ... ", "dissemination" and a "positive MRI", etc. Later they were revised again in 2010. McDonald's criteria are the standard ...
CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average ... T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional ... Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase ... "Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes". Frontiers in ...
... has studied the role of T lymphocytes in the immune system. In particular he has addressed the contribution ... Questions concerned with the role of positive and negative selection of developing T cells by peptide-MHC complexes in the ... Nature 261, 141 (1976). Allo-MHC-restricted CD4 and CD8 T cells in hemopoietic chimeras reveal plasticity of MHC-restricted ... Harald von Boehmer (born November 30, 1942) is a German/Swiss immunologist best known for his work on T lymphocytes. The ...
... hemizygous mutant males had decreased CD4-positive and CD8-positive T cell numbers. RBBP7 has been shown to interact with: ... ". "Peripheral blood lymphocytes data for Rbbp7". Wellcome Trust Sanger Institute. [dead link] Gerdin AK (2010). "The Sanger ...
For example, miR-181a was found to play a role in the positive selection of T lymphocytes. The thymus contributes fewer cells ... These thymocytes will then express both CD4 and CD8 and progresses to the double positive (DP) stage where selection of the α- ... If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4+, single positive cell. But, if ... A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated ...
Women who test positive for thyroid antibodies may be at increased risk of developing symptoms associated with postpartum ... CD8 ratio) TSH-receptor antibodies (TSH-R Abs) This condition is commonly undiagnosed by physicians due to either unfamiliarity ... increase in TPOAb subclasses IgG1-IgG3 lymphocyte infiltration and follicle formation within thyroid gland (Hashimoto's ...
CD8+), and finally mature to single-positive (CD4+CD8− or CD4−CD8+) thymocytes that are then released from the thymus to ... A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated ... The process of positive selection takes a number of days.[34] Double-positive thymocytes (CD4+/CD8+) move deep into the thymic ... A thymocyte's fate is determined during positive selection. Double-positive cells (CD4+/CD8+) that interact well with MHC class ...
This is called positive selection. During positive selection, co-receptors CD4 and CD8 initiate a signaling cascade following ... When primary lymphocytes are developing and differentiating in the thymus or bone marrow, T cells die by apoptosis if they ... It follows that MHC restriction is imposed by CD4 and CD8 co-receptors during positive selection of T cell selection. A ... T cell maturation involves two distinct developmental stages: positive selection and negative selection. Positive selection ...
Homozygous mutant females had decreased bone mineral content, heart weight, lean body mass and CD8-positive, alpha-beta memory ... "Peripheral blood lymphocytes data for Arl4d". Wellcome Trust Sanger Institute. "Heart weight data for Arl4d". Wellcome Trust ... "Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients ...
The polymorphous infiltrate consists of lymphocytes of moderate size with pale/clear cytoplasm and smaller reactive lymphocytes ... AITL typically has the phenotype of a mixture of CD4+ and CD8+ T-cells, with a CD4:CD8 ratio greater than unity. Polyclonal ... and positive rheumatoid factor. The normal architecture of a lymph node is partially effaced by a polymorphous infiltrate and ...
... fever and positive lymphocyte transformation test in a patient on irbesartan". The British Journal of Dermatology. 155 (2): 491 ... CD8(+), and CD4(+)CD8(+) T-cell clones from patients with carbamazopine hypersensitivity Herbal medicines and acute medical ... fever and positive lymphocyte transformation test in a patient on irbesartan Serious carbamazepine-induced hypersensitivity ... Owen, A; Goldring, C; Morgan, P; Park, BK; Pirmohamed, M (August 2006). "Induction of P-glycoprotein in lymphocytes by ...
Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-receptors on T lymphocytes, and the antigen ... MHC restriction occurs during lymphocyte development in the thymus through a process known as positive selection. T cells that ... This means in contrast to CD8/TCR interaction that activates Tc lymphocytes, NK cells becomes deactivated when bound to MHC I. ... It presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition ...
MAIT cells were initially specified as T cells that do not express the TCR co-receptors CD4 or CD8 on the cell surface. However ... MAIT cells constitute a subset of αβ T lymphocytes characterized by a semi-invariant T cell receptor alpha (TCRα) chain. The ... Here, T cells rearrange their TCRs and are subjected to TCR affinity tests as a part of positive selection and negative ... MAIT cells are most common in the liver, where they usually comprise 20-40% of the T lymphocyte population. Interestingly, the ...
It measures the density of two T lymphocyte populations (CD3/CD8, CD3/CD45RO or CD8/CD45RO) in the center and at the periphery ... It is based on Jerome Galon's finding from 2006 which revealed the major positive role of cytotoxic and memory T cells for ...
CD8-positive) subset, similar populations appear to exist for both the helper T cells (CD4-positive) and the cytotoxic T cells ... Memory T cells are a subset of infection- and cancer-fighting T cells (also known as a T lymphocyte) that have previously ... Although CD8 virtual memory T cells were the first to be described, it is now known that CD4 virtual memory cells also exist. ... This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens. Historically, ...
一个T细胞的命运就在阳性选择的过程中被决定。在双阳性(CD4+/CD8+)T细胞中,能够与MHC-II分子结合得较好的将成为CD4+细胞,而和MHC-I分子有更高亲和力的将成为CD8+细胞。将成为CD4+细胞的细胞将会逐渐下调自己的CD8,最终成为单阳性 ... T细胞(英語:T cell、T lymphocyte)是淋巴细胞的一种,在免疫反應中扮演着重要
If activated cytotoxic CD8+ T cells recognize them, the T cells secrete various toxins that cause the lysis or apoptosis of the ... As of 2015 mass spectrometry resolution is insufficient to exclude many false positives from the pool of peptides that may be ... They become activated and start to secrete cytokines, substances that activate cytotoxic T lymphocytes (CTL), antibody- ... Cytotoxic T lymphocytes that recognize these antigens may be able to destroy tumor cells.[15] ...
May, MT; Ingle, SM (2011 Dec). "Life expectancy of HIV-positive adults: a review". Sexual health 8 (4): 526-33. PMID 22127039. ... A viremia aguda está case invariablemente asociada coa activación das células T CD8+ (ou T citotóxicas), que matan ás células ... Alimonti JB, Ball TB, Fowke KR (2003). "Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection ... Unha boa resposta das células T CD8+ está asociada cunha progresión máis lenta da enfermidade e un mellor prognóstico, aínda ...
positive regulation of leukocyte migration. • platelet degranulation. • regulation of integrin activation. • cell adhesion. • ... PSGL-1 is situated on various hematopoietic cells such as neutrophils, eosinophils, lymphocytes, and monocytes, in which it ... positive regulation of platelet activation. • leukocyte migration. • response to lipopolysaccharide. • calcium-dependent cell- ... positive regulation of phosphatidylinositol 3-kinase signaling. • inflammatory response. • calcium-mediated signaling using ...
positive regulation of T cell proliferation. • regulation of defense response to virus by host. • positive regulation of ... CD8+ memory T cell number is controlled by a balance between IL-15 and IL-2. When IL-15 binds its receptor, JAK kinase, STAT3, ... In rodent lymphocytes, IL-15 prevents apoptosis by inducing BCL2L1/BCL-x(L), an inhibitor of the apoptosis pathway.[10] In ... positive regulation of immune response. • inflammatory response. • immune response. • positive regulation of cell proliferation ...
B lymphocytes or T lymphocytes). Cytogenetic testing on the marrow samples can help classify disease and predict how aggressive ... Person with t(9,22) positive-ALL (30% of adult ALL cases) and other Bcr-abl-rearranged leukemias are more likely to have a poor ... CD2, CD3, CD4, CD5, CD7, CD8 - + TdT + + CytogeneticsEdit. Cytogenetic analysis has shown different proportions and frequencies ... on the cell surface can help differentiate malignant lymphocyte cells from reactive lymphocytes, white blood cells that are ...
LymphocytesEdit. Main article: Lymphocyte. T and B lymphocytes are the cells of the adaptive immune system. The human body has ... Endogenous antigens are typically displayed on MHC class I molecules, and activate CD8+ cytotoxic T-cells. With the exception ... immunity as they are uniquely capable of migrating to follicular B cells in secondary lymphoid organs and provide them positive ... In jawless fishes, two subsets of lymphocytes use variable lymphocyte receptors (VLRs) for antigen binding.[33] Diversity is ...
positive regulation of transcription, DNA-templated. • cellular response to lithium ion. • cell adhesion. • extracellular ... Lymphocyte homing receptor: CD44. *L-selectin. *integrin (VLA-4, LFA-1). *Carcinoembryonic antigen ... positive regulation of transcription factor import into nucleus. • pituitary gland development. • response to toxic substance. ...
positive regulation of flagellated sperm motility involved in capacitation. • lymphocyte migration. • T cell migration. • ... positive regulation of cytosolic calcium ion concentration. • positive regulation of epithelial cell migration. • dendritic ... positive regulation of dendritic cell chemotaxis. • signal transduction. • calcium-mediated signaling. • chemotaxis. • cell ... 1997). "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". J. Biol. Chem. 272 ( ...
limfocyty T CD8+CD25+Foxp3+[26] - subpopulacja analogiczna do poprzednio wymienionej, jednak występująca wśród limfocytów T CD8 ... A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. „J Exp Med". 144 ... Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive ... limfocyty CD8+CD28−[27] - utożsamiane z wcześniejszymi limfocytami Ts, również nie posiadają ekspresji czynnika Foxp3. ...
"The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by ... positive regulation of natural killer cell mediated cytotoxicity. • antigen processing and presentation of exogenous peptide ... LAG3 also helps maintain CD8+ T cells in a tolerogenic state[9] and, working with PD-1, helps maintain CD8 exhaustion during ... "Entrez Gene: LAG3 lymphocyte-activation gene 3".. *^ a b c Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas ...
Alloreactive killer T cells, also called cytotoxic T lymphocytes (CTLs), have CD8 receptors that dock to the transplanted ... type B-positive with a type AB-positive graft) require eventual retransplantation, the recipient may receive a new organ of ... Lymphocytes include two classes that enact adaptive immunity, also called specific immunity. Lymphocytes of specific immunity T ... There is a risk of graft-versus-host disease (GVHD), however, whereby mature lymphocytes entering with marrow recognize the new ...
... also called CD8 positive- or cytotoxic T-cells) that destroy cells. MHC class I proteins associate with β2-microglobulin, which ... HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. ... A representative cellular assay is the mixed lymphocyte culture (MLC) and used to determine the HLA class II types.[20] The ...
As naïve CD8+ T cells have no true bias towards foreign sources, these T cells must rely on the activation of CD28 for ... The key Th2 transcription factors are STAT6 and GATA3.[10] IL-4 is the positive feedback cytokine for Th2 cells differentiation ... These effects are primarily due to the loss of any helper T cell that can interact with the B lymphocyte correctly. Another ... CD8+ T cells are not stimulated as effectively during the AIDS stage of HIV infection, making AIDS patients very susceptible to ...
A thymocyte's fate is determined during positive selection. Double-positive cells (CD4+/CD8+) that interact well with MHC class ... A T cell is a type of lymphocyte which develops in the thymus gland and plays a central role in the immune response. T cells ... Double-positive thymocytes (CD4+/CD8+) move deep into the thymic cortex, where they are presented with self-antigens. These ... If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4+, single positive cell.[6] ...
Indeed, up to 32% of the healthy population may test positive, but not require treatment.[29][30] Conversely, because ... All of these lymphocytes act, at least in part, by secreting IL-10 and other suppressive cytokines. ... "CD8 T Cell Exhaustion in Human Visceral Leishmaniasis". J. Infect. Dis. 209 (2): 290-99. doi:10.1093/infdis/jit401. PMC ... A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and ...
positive regulation of G-protein coupled receptor protein signaling pathway. • immune response. • neuropeptide signaling ... D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes". ...
positive regulation of cell proliferation. • T cell activation. • cell adhesion. • Viral entry. • regulation of insulin ... "CD26/dipeptidyl peptidase IV in lymphocyte growth regulation". Advances in Experimental Medicine and Biology. 421: 127-40. doi: ...
positive regulation of interleukin-4 production. • positive regulation of interleukin-10 production. • positive regulation of T ... CD40 ligand is primarily expressed on activated CD4+ T lymphocytes but is also found in a soluble form. While CD40L was ... positive regulation of endothelial cell apoptotic process. • B cell proliferation. • isotype switching. • immune response. • ... positive regulation of interleukin-12 production. • regulation of immunoglobulin secretion. • immunoglobulin secretion. • ...
CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling.[ ... positive regulation of cell growth. • positive regulation of B cell proliferation. • positive regulation of vasoconstriction. • ... positive regulation of insulin secretion. • negative regulation of bone resorption. • NAD metabolic process. • positive ... positive regulation of cytosolic calcium ion concentration. • response to progesterone. • female pregnancy. • negative ...
positive regulation of T cell proliferation. • membrane to membrane docking. • regulation of immune response. • leukocyte ... The VCAM-1 protein mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also ...
Zwahlen M, Egger M (2006) (PDF). Progression and mortality of untreated HIV-positive individuals living in resource-limited ... Mwitikio bora wa seli za CD8+ T umehusishwa na kupungua kwa mwendo wa ugonjwa na pia prognosi bora zaidi, ingawa mwitikio huu ... Alimonti JB, Ball TB, Fowke KR (2003). "Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection ... May, MT; Ingle, SM (2011 Dec). "Life expectancy of HIV-positive adults: a review". Sexual health 8 (4): 526-33. doi:10.1071/ ...
positive regulation of cytokinesis. • chemokine-mediated signaling pathway. • Хемотаксис. • B cell activation. • G-protein ... Lipp M., Müller G. Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking (англ.) // ... positive regulation of cytosolic calcium ion concentration. • calcium-mediated signaling. • cell chemotaxis. ... and CXCR5-expressing lymphocytes and immature dendritic cells to migrate (англ.) // Blood (англ.)русск. : journal. - American ...
positive regulation of tumor necrosis factor production. • CD8-positive, alpha-beta T cell differentiation involved in immune ... and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops.[11][12] IFNγ is ... positive regulation of exosomal secretion. • positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell ... positive regulation of neuron differentiation. • positive regulation of T cell proliferation. • cell cycle arrest. • positive ...
A sizable fraction of individuals who have gluten ataxia have signs of GSE (either CD or elevated intraepitheal lymphocytes) ... haplotypes has been under positive selection, and appears to be the most characteristic HLA type in NW Europeans indicating an ... Decreased expression of: CD8, CD4, TCR-alpha/beta. Clonal T-cell expansion in RCD2 is not manageable with steroids (see: RCD 1 ... Antibodies to this protein correlated with levels of lymphocyte infiltration into Islet regions of the pancreas.[52] ...
positive regulation of cell proliferation. • positive regulation of ERK1 and ERK2 cascade. • phagocytosis. • lymphocyte ... positive regulation of JNK cascade. • cell adhesion. • negative regulation of CD40 signaling pathway. • negative regulation of ... positive regulation of activated T cell proliferation. • negative regulation of interleukin-12 production. • natural killer ... positive regulation of interferon-gamma secretion. • myeloid dendritic cell activation involved in immune response. • ...
Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named ... The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.[7] ... CD8). By. development/. marker. *TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) ... of normal germinal center lymphocytes. Tumor cells possess small amounts of basophilic cytoplasm with three to four small ...
Small resting lymphocytes mixed with variable number of large activated cells. Lymph nodes are diffusely effaced[1] CD5, ... The TCR gene transcripts are normally positive for ANKL. [5] Current Research is attempting to find the causation of ANKL. So ... CD8). By. development/. marker. *TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) ... Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cells. The lymphocytic ...
CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses. Mayumi ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ...
In order to determine the fine structural differences and labeling by immunoferritin particles of CD4-positive (CD4+) and CD8 ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... and CD8 positive (CD8+) cells at the ultrastructural level, short term cultured lymphocytes from eight healthy donors ... Sera of eight donors were all positive on the particle agglutination (PA) test, but only of the four of the eight were positive ...
CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. / Laing, S. T.; ... CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Journal of ... Laing, S. T., Griffey, S. M., Moreno, M. E., & Stoddart, C. A. (2015). CD8-positive lymphocytes in graft-versus-host disease of ... Laing, S. T. ; Griffey, Stephen M ; Moreno, M. E. ; Stoddart, C. A. / CD8-positive lymphocytes in graft-versus-host disease of ...
What is Cd8-positive t-lymphocytes? Meaning of Cd8-positive t-lymphocytes medical term. What does Cd8-positive t-lymphocytes ... Looking for online definition of Cd8-positive t-lymphocytes in the Medical Dictionary? Cd8-positive t-lymphocytes explanation ... Cd8-positive t-lymphocytes , definition of Cd8-positive t-lymphocytes by Medical dictionary https://medical-dictionary. ... redirected from Cd8-positive t-lymphocytes). Also found in: Dictionary, Thesaurus, Encyclopedia. cytotoxic T cell. n.. See ...
PD-L1−/CD8Low, 22.7%; PD-L1+/CD8Low, 2.3%; PD-L1−/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+ and MSI- ... Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in ... PD-L1−/CD8High showed the best overall survival (OS) and PD-L1−/CD8Low the worst (P , 0.001). PD-L1 expression alone was not ... We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 ...
CD8-positive T-lymphocytes Remove constraint Subject: CD8-positive T-lymphocytes Subject humans Remove constraint Subject: ... CD8-positive T-lymphocytes; animal injuries; animal models; biotin; cerebrospinal fluid; cytokines; enzyme-linked immunosorbent ... 1. CD8 T cell-derived perforin aggravates secondary spinal cord injury through destroying the blood-spinal cord barrier ...
CD8-Positive T-Lymphocytes / immunology * Cystadenocarcinoma, Serous / genetics * Cystadenocarcinoma, Serous / immunology* * ... number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer Oncotarget. 2016 Mar ... harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes ( ...
T1 - Adaptive cell-mediated cytotoxicity against allogeneic targets by CD8-positive lymphocytes of rainbow trout (Oncorhynchus ... Adaptive cell-mediated cytotoxicity against allogeneic targets by CD8-positive lymphocytes of rainbow trout (Oncorhynchus ... Adaptive cell-mediated cytotoxicity against allogeneic targets by CD8-positive lymphocytes of rainbow trout (Oncorhynchus ... title = "Adaptive cell-mediated cytotoxicity against allogeneic targets by CD8-positive lymphocytes of rainbow trout ( ...
... were used for purification of CD8+CD28+ (by positive selection) and CD8+CD28− (by negative selection) T lymphocytes; the CD4+ ... Purification of CD8+CD28+, CD8+CD28−, and CD4+CD25+ T lymphocytes. Lymphocytes from surgical specimens were purified filtering ... of CD8+CD28+, CD8+CD28−, or CD4+CD25+ T lymphocytes (1 × 105 cells/well). The experiments with CD8+CD28− T cells were performed ... "Analysis of Frequency and Functional Activity of Telomerase-Specific CD8+ T Lymphocytes and CD8+ T Suppressor Lymphocytes in ...
CD4-Positive T-Lymphocytes. CD8-Positive T-Lymphocytes. Biological Markers. Lamivudine. Reverse Transcriptase Inhibitors. Anti- ... cytotoxic T cell lymphocyte function and CD4 T helper function correlates with the patterns of cellular immune antiviral ... a cohort of HIV negative individuals that tested with the Options Project to use as a comparison group with the HIV positive ...
CD8-Positive T-Lymphocytes. Saliva. Blood. Cervix Uteri. Vagina. Acute Infection. Additional relevant MeSH terms: ... or if they have recently become HIV-positive. ...
CD4-Positive T-Lymphocytes: immunology. *CD8-Positive T-Lymphocytes. *CD8-Positive T-Lymphocytes: immunology ... Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ ... Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor ... TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors.. *Maccalli C ...
Selective depletion of CD8 positive T-lymphocytes for prevention of graft-versus-host disease following allogeneic bone marrow ... Selective depletion of CD8 positive T-lymphocytes for prevention of graft-versus-host disease following allogeneic bone marrow ... Selective depletion of CD8 positive T-lymphocytes for prevention of graft-versus-host disease following allogeneic bone marrow ... T1 - Selective depletion of CD8 positive T-lymphocytes for prevention of graft-versus-host disease following allogeneic bone ...
Here, we study the elimination kinetics of viral antigen-positive lymphocytes by antiviral CD8(+) T cells using flow cytometry ... Unexpectedly, the elimination kinetics of antigen-positive lymphocytes was not significantly impaired in mice deficient in ... For viruses with a particular tropism for lymphocytes, such as Epstein-Barr virus or HIV, our results illustrate how ... effectively CD8(+) T cell-mediated elimination of target cells can potentially contribute to virus control and ...
Fingerprint Dive into the research topics of Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the ... T1 - Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the urinary bladder recurrence of urothelial ... Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the urinary bladder recurrence of urothelial ... Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the urinary bladder recurrence of urothelial ...
CD8-positive T-lymphocytes Remove constraint Subject: CD8-positive T-lymphocytes Subject animal injuries Remove constraint ... CD8-positive T-lymphocytes; animal injuries; animal models; biotin; cerebrospinal fluid; cytokines; enzyme-linked immunosorbent ... 1. CD8 T cell-derived perforin aggravates secondary spinal cord injury through destroying the blood-spinal cord barrier ...
High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B,... High levels of CD8-positive lymphocytes expressing ... However, there were significantly higher concentrations of CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67(+) lymphocytes in the ... and CD8(+)Ki-67(+) lymphocytes. This finding allowed us to conclude that CD8(+) lymphocytes expressing high levels of CD45R0, ... whereas low concentrations of CD8(+) granzyme B(+) and CD8(+)Ki-67(+) lymphocytes may be associated with poor prognosis. ...
title = "Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... T1 - Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ...
CD8-Positive T-Lymphocytes / drug effects * CD8-Positive T-Lymphocytes / immunology* * Cell Differentiation / immunology* ... might promote BMCs to differentiate into CD8(+) T lymphocytes in lung tissue via up-regulating Notch1 expression. This may ... Importantly, lung can be as one athymus tissue for the BMCs to differentiate into CD8(+) T cells. Notch1 plays a critical role ... Suppressor of cytokine signaling 3 promotes bone marrow cells to differentiate into CD8+ T lymphocytes in lung tissue via up- ...
CD8-Positive T-Lymphocytes. Pereyra F, Jia X, McLaren PJ, et al. "The major genetic determinants of HIV-1 control affect HLA ...
T lymphocytes infiltrating advanced grades of cervical neoplasia. CD8-positive cells are recruited to invasion ... HPV16-specific cytotoxic T lymphocyte responses are detected in all HPV16-positive cervical cancer patients ... Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes ... Antigen-Specific CD8 T Cells Can Eliminate Antigen-Bearing Keratinocytes with Clonogenic Potential via an IFN-γ-Dependent ...
... lymphocyte subpopulations and plasma cortisol concentration in peripheral blood were assessed in 19 healthy subjects. The ... The effects of exercise distribution on lymphocyte count, ... CD4-Positive T-Lymphocytes. CD8-Positive T-Lymphocytes. ... The effects of exercise distribution on lymphocyte count, lymphocyte subpopulations and plasma cortisol concentration in ... CD4+ and CD8+ lymphocytes. The S2 variables statistically significant from B were: total lymphocyte count (P , 0.01), CD3+ T- ...
An ultrastructural study on the lymphocytes from peripheral blood samples from 20 healthy adult Arabian oryx (Oryx leucocoryx) ... Cd8-positive T-lymphocytes. A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted ... CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. ... For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also ...
... in a significant increase of CD8-positive lymphocytes within the tumor microenvironment but a decrease in FOXP3-positive T cell ... No changes were reported for circulating CD8-positive lymphocytes. Metabolomic profiling of pre- and postanesthesia plasma ... while viability and apoptosis of circulating CD4-positive lymphocytes were significantly affected by propofol administration [8 ... Lower levels of oxidative DNA damage and apoptosis in lymphocytes from patients undergoing surgery with propofol anesthesia. ...
CD19-positive B lymphocytes; c, CD3-positive total T lymphocytes; d, CD8-positive T cells; e, CD4-positive T cells; f, CD4+CD44 ... Discrete lymphocyte compartments in TNFR-deficient NZM 2328 mice. Total spleen lymphocytes were increased in DKO mice, largely ... A, Proportional increase of CD4+ and decrease of CD8+ T cells in p55/p75 DKO mice. The numbers shown in quadrants of each plot ... The numbers shown in the upper right quadrant of each plot indicate percentage of total lymphocytes. C, Increased CD4+ ...
Many T lymphocytes were identified by these authors positive to CD4 and CD8. Macrophages and T lymphocytes demonstrated a ... The foam cells of monocyte/macrophage origin are positive for KP1, HAM56, CD11b and CD68 as pointed out by Nakashiro et al. in ... Under microscope, the cellular infiltrate includes neutrophils, lymphocytes, plasma cells, erythrocytes, hemosiderin-laden ...
Cd8-positive T-lymphocytes. A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted ... T-lymphocytes. Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, ... They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. ... CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the ...
CD4 Lymphocyte Count / drug effects. CD8-Positive T-Lymphocytes. Capillary Leak Syndrome / chemically induced. Disease ... Lymphocyte Count / drug effects. Male. Middle Aged. Mouth Neoplasms / etiology, immunology, therapy*. Remission Induction. ... Seventeen had CD4+ lymphocyte counts less than 200/mm3. RESULTS: The most common adverse effects included headache in 78%, ... IL-4 produced minimal anti-tumor effects in AIDS-KS with one partial remission in a patient with CD4 lymphocyte counts over 200 ...
Results were expressed as percentages of total number of gated lymphocytes. The percentages of CD4 and CD8 positive cells were ... As a positive control, one animal each from the HIV-1 infected (open black structure) and HIV-1 and LASER ART (open green ... In addition, as positive controls, two animals from the HIV-1 infected group, one from the LASER ART alone treatment group and ... 19)12 including the persistence of human adult lymphocytes in mouse plasma and tissue (Fig. 4). As such, these proof-of-concept ...
... there is infiltration by atypical CD8-positive T lymphocytes. ...
  • Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. (
  • There is little literature about peripheral blood lymphocytes (PBL). (
  • Flow Cyt: Human peripheral blood lymphocytes. (
  • The effects of exercise distribution on lymphocyte count, lymphocyte subpopulations and plasma cortisol concentration in peripheral blood were assessed in 19 healthy subjects. (
  • lymphocytes from peripheral blood samples from 20 healthy adult Arabian oryx (Oryx leucocoryx) was undertaken. (
  • Preliminary results indicate that TCT has positive effects on some functions of CD4 T lymphocytes ( 18 ), but the properties of other peripheral blood mononuclear cell (PBMC) subsets have not been well studied. (
  • Subsets of peripheral blood lymphocytes were analysed in 31 patients. (
  • To investigate the specific cell types which may respond to Barodon, two-color fluorescence flow cytometry was used with monoclonal antibodies (mAbs) of different isotypes that reacted with lymphocytes from peripheral blood and lymphoid tissues from treated feeder pigs. (
  • Lysed human peripheral blood from a normal donor was labeled with CD4-Pacific Blue™ and CD8-Pacific Orange™ direct conjugates, and then labeled with the SYTOX® Orange Dead Cell Stain Kit before acquisition on the Attune® Acoustic Focusing Cytometer. (
  • In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. (
  • As a result all potential CD8 T cell epitopes contained in these proteins were provided by the complete pools and, therefore, unlike with single epitopes, testing was independent of donor HLA type. (
  • Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. (
  • Together, our data show that a combination of DNA and MVA immunization induced robust, durable, multifunctional CD4(+) and CD8(+) responses in baboons targeting multiple HIV epitopes that may home to mucosal sites. (
  • Five well-conserved novel CD8(+) T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. (
  • Two epitopes aa129-aa137 and aa131-aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8(+) T-cell response. (
  • The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8(+) T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans. (
  • We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. (
  • Here we analyze the expression of the three IL-2R chains by CD4 T, CD8 T, B, and natural killer (NK) lymphocytes, as well as monocytes, of HIV-infected patients with high viral load. (
  • lymphocytes ranged in size from 2-3.5 µm and exhibited the typical repertoire of organelles found in small lymphocytes of other animals but showed no evidence of azurophilic granules. (
  • Small lymphocytes exhibited short, thick microvilli, whereas medium-sized lymphocytes had long thin microvilli, a single nucleolus and occasionally azurophilic granules and multivesicular bodies. (
  • The unprecedented observation was made that CD8 + CD28 − T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. (
  • Unexpectedly, the elimination kinetics of antigen-positive lymphocytes was not significantly impaired in mice deficient in either perforin-, CD95 ligand- or TNF-mediated cytotoxicity. (
  • We here compared the effect of GCS-100 with that of LacNAc on the cytotoxicity and cytokine secretion by CD8 + and CD4 + human TIL on ex vivo stimulation, and tested the therapeutic potential of GCS-100 in a murine tumor model. (
  • In the skin and liver, cell death was associated with lymphocytes that reacted with anti-human CD45, CD3 and CD8 antibodies, consistent with a diagnosis of graft-versus-host disease (GvHD). (
  • Lymphocytes that matures into a plasma cell to create antibodies. (
  • Lymphocytes that secrete antibodies. (
  • If these reactions are responsible for causing adverse events to vaccines, then these reactions would be extensions of the beneficial responses to vaccines, which are mediated by protective immunoglobulin G (IgG) antibodies and T-lymphocyte responses. (
  • HIV antibodies were undetectable, and CD4/CD8 lymphocyte counts were within reference ranges. (
  • Recent studies have demonstrated the critical role of virus-specific CD8 + CTL responses in controlling HIV-1 replication in humans and simian immunodeficiency virus (SIV) replication in rhesus monkeys ( 1-5 ). (
  • This was associated with a decreased percentage of NKG2D-positive thymocytes, which expressed a less mature phenotype than in normal thymus. (
  • Immature thymocytes, both triple negatives (αβTCR − CD4 − CD8 − ) and triple positives (αβTCR + CD4 + CD8 + ), participate in intimate cortical lymphoepithelial complexes ( 7 , 14 , 16 , 48 ). (
  • As thymocytes move through the thymus, from triple negatives to single positives, they produce a T-cell antigen receptor (αβTCR) on their cell surface (Fig. 1 ). (
  • Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. (
  • Although CD4 + CD25 + T cell tumor infiltration has been extensively studied, only scanty information exists concerning the presence and function of CD8 + CD28 − Treg in human tumors ( 6 , 7 ). (
  • there is infiltration by atypical CD8-positive T lymphocytes. (
  • We found that the degree of infiltration by CD25 + and intratumoral OX40 + lymphocytes showed a tendency to decrease in thicker melanomas. (
  • For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis ( P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40 + lymphocyte infiltration had an impact on survival also in multivariate analysis ( P = 0.035). (
  • Marrow transplanted immunocompromised patients with cytomegalovirus (CMV) viral infection will be treated with CMV activated T-Lymphocytes. (
  • These results suggested that both lymphocyte subpopulations contribute to viral clearance, with either subpopulation alone being sufficient. (
  • Peripheral lymphocyte subset analysis revealed the existence of T lymphocytes double positive for CD4 and CD8 markers. (
  • T-Lymphocytes, Cytotoxic" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • Here, we examined the prognostic role of pretreatment white blood cell (WBC) count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL) and myeloperoxidase+ tumor-associated neutrophils (TANs) in patients with anal squamous cell carcinoma (ASCC) treated with definitive chemoradiotherapy (CRT). (
  • Jennings, S. R., Bonneau, R. H., Smith, P. M., Wolcott, R. M. & Chervenak, R. CD4-positive T lymphocytes are required for the generation of the primary but not the secondary CD8-positive cytolytic T lymphocyte response to herpes simplex virus in C57BL/6 mice. (
  • The cytolytic T-lymphocyte (CTL) response to respiratory infection with equine herpesvirus 1 (EHV-1) in CBA ( H-2 k ) mice was investigated. (
  • Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative bacteria, fungi/yeast and parasites. (
  • The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients' survival in cutaneous malignant melanoma. (
  • CD25 is highly expressed on regulatory CD4-positive T lymphocytes and undetected on resting CD8 positive lymphocytes. (
  • However, all activated T lymphocytes express the CD25 protein. (
  • Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric. (
  • We co-assessed PD-L1 expression and CD8 + tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 microenvironment immune types. (
  • These findings support the close relationship between PD-L1/CD8 status based immune types and EBV + , MSI-H GCs, and their prognostic significance in stage II/III GCs. (
  • An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. (
  • Although cancers express tumor-associated Ags ( 1 , 2 ) and are infiltrated by tumor-specific T lymphocytes ( 3 , 4 ), they are able to evade immune surveillance. (
  • T lymphocyte development in the thymus is a complex process essential for the formation of the immune system. (
  • Homing of B lymphocytes into specialized microenvironments within secondary lymphoid tissues is essential for normal immune function, yet the molecular cues guiding this cellular traffic are not well defined. (
  • T lymphocytes were separated by direct positive panning on anti-CD3 monoclonal antibody-coated flasks (MicroCELLector, Applied Immune Sciences) according to the manufacturer's instructions. (
  • The ISF was determined by several important innate (total complement and lysozyme activity, neutrophil function) and adaptive immune parameters (lymphocytes, IgA and IgG, and response to the flu vaccine). (
  • Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. (
  • Objective: Tumor-infiltrate lymphocytes (TIL) have been associated with favorable outcomes in various tumors including urothelial carcinoma (UC). (
  • In patients with advanced cancer, tumors progress despite the presence of tumor-infiltrating lymphocytes (TIL). (
  • Organ specificity of lymphocyte migration: mediation by highly selective lymphocyte interaction with organ-specific determinants on high endothelial venules. (
  • Recent studies by Blotnick et al 6 have revealed that T lymphocytes in atherosclerotic lesions produce smooth muscle growth factors, including HB-EGF, indicating that T cell-derived smooth muscle mitogens, in concert with other cytokines, may modulate fibroproliferative processes in the vessel wall. (
  • Figure 14 CD20, a B lymphocyte marker, stains occasional perivascular B-lymphocytes. (
  • A CD20 and CD5 immunohistochemical stain are positive, while a BCL1 (and SOX-11, not shown) are negative, thus far, consistent with CLL/SLL. (
  • To study the role of cytotoxic and mitotic active CD8(+) lymphocytes in lymph nodes during HIV infection we examined 28 formalin-fixed, paraffin-embedded lymph nodes sampled from 1984 to 1986 from 21 HIV-seropositive patients and seven HIV-negative patients. (
  • This finding allowed us to conclude that CD8(+) lymphocytes expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV patients are not related to increased mortality, whereas low concentrations of CD8(+) granzyme B(+) and CD8(+)Ki-67(+) lymphocytes may be associated with poor prognosis. (
  • Here we describe a chemokine, B Lymphocyte Chemoattractant (BLC), that is highly expressed in the follicles of Peyer's patches, spleen and lymph nodes. (
  • Immunohistochemistry ( PD-L1 , CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. (
  • Furthermore, available tumor specimens from 27 patients were further analyzed for number of CD8 + tumor infiltrating lymphocytes (TIL) using immunohistochemistry. (
  • The frequency of epitope-specific pentamer(+) CD8(+) T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. (
  • CONCLUSION Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS. (
  • Sun, J. C. & Bevan, M. J. Defective CD8 T cell memory following acute infection without CD4 T cell help. (
  • Single-platform technology (SPT) is designed to enable de- system and managing the health care of persons infected with terminations of both absolute and percentage lymphocyte sub- human immunodeficiency virus (HIV) ( 1-4 ). (
  • Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T-lymphotropic virus type I . Biomedical Research (India) , 18 (2), 83-88. (
  • This phase I/Ib trial studies the side effects and best dose of utomilumab and how well it works with CD8-positive T-lymphocyte (T-cell infusion) and aldesleukin in treating patients with ovarian cancer that has come back. (
  • CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. (
  • Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. (
  • OBJECTIVES: The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART). (
  • Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8(+) T cell immunity in children is currently unknown. (
  • NK T lymphocytes may be classified into those that are positively selected by CD1d, a nonclassical class I molecule (for review see reference 1), and those that are CD1d independent. (
  • The CD8 molecule consists of either an α/β heterodimer or an α/α homodimer. (
  • Here we compared the virus-specific CD8(+) T cell immunity in children vaccinated annually with that in unvaccinated children. (
  • However, there were significantly higher concentrations of CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67(+) lymphocytes in the HIV patients compared with the control group. (
  • As reported in JAMA Oncology by Goode et al in the Ovarian Tumor Tissue Analysis Consortium, higher levels of cytotoxic CD8-positive tumor-infiltrating lymphocytes were associated with significantly improved overall survival among women with high-grade serous ovarian carcinomas. (
  • With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. (
  • The separated PBL fractions were characterized by RT-PCR analysis using specific primers for the amplification of trout IgM heavy chain constant region (CH1), T cell receptor alpha chain (TCRα), CD8α and major histocompatibility complex (MHC) class I gene fragments. (
  • The invention provides methods for identifying agents which modulate the interaction of a chemokine receptor of previously unknown function, Burkitt's Lymphoma Receptor 1 (BLR1), with its ligand, B Lymphocyte Chemoattractant (BLC). (
  • Pembrolizumab (Keytruda) showed activity in previously treated patients with advanced programmed cell death ligand 1 (PD-L1)-positive endometrial cancer in a cohort of the phase Ib KEYNOTE-028 study. (