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.
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.
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.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
A classification of lymphocytes based on structurally or functionally different populations of cells.
The number of LYMPHOCYTES per unit volume of BLOOD.
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.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An encapsulated lymphatic organ through which venous blood filters.
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 soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
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).
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.
Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.
Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
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 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 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)
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.
Antibodies produced by a single clone of cells.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A 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.
Established cell cultures that have the potential to propagate indefinitely.
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.
Sites on an antigen that interact with specific antibodies.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A 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.
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.
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.
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.
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.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
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.
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 transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
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.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
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.
The major group of transplantation antigens in the mouse.
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.
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)
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.
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.
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.
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.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
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.
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).
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 group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
The 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)
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.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
T-cell receptors composed of CD3-associated 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.
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.)
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.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
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)
Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS.
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.
Substances that are recognized by the immune system and induce an immune reaction.
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.
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).
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Substances elaborated by viruses that have antigenic activity.
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.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A 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.
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.
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.
A cell line derived from cultured tumor 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.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Antigens 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.
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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
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.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A class of lymphocytes characterized by the lack of surface markers specific for either T or B lymphocytes.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
Proteins prepared by recombinant DNA technology.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Adherence of cells to surfaces or to other cells.
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.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
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.
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).
Unstable isotopes of chromium that decay or disintegrate emitting radiation. Cr atoms with atomic weights of 46-49, 51, 55, and 56 are radioactive chromium isotopes.
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.
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.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
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.
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.
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.
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.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The rate dynamics in chemical or physical systems.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
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.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
A general term for various neoplastic diseases of the lymphoid tissue.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Reduction in the number of lymphocytes.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
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.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
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.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related 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.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A protein extracted from boiled culture of tubercle bacilli (MYCOBACTERIUM TUBERCULOSIS). It is used in the tuberculin skin test (TUBERCULIN TEST) for the diagnosis of tuberculosis infection in asymptomatic persons.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
The largest lymphatic vessel that passes through the chest and drains into the SUBCLAVIAN VEIN.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.
The type species of ARENAVIRUS, part of the Old World Arenaviruses (ARENAVIRUSES, OLD WORLD), producing a silent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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.
A unifocal malignant tumor that consists of atypical pathological MAST CELLS without systemic involvement. It causes local destructive growth in organs other than in skin or bone marrow.

Cell-mediated immunity: dealing a direct blow to pathogens. (1/8493)

Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis.  (+info)

Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL. (2/8493)

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/delta TCR, specific for the disaccharide, even on glycolipids. The crystal structure of Kb/RGY8-6H-Gal2 now demonstrates that the peptide and H-2Kb structures are unaffected by the peptide glycosylation, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of the Kb/RGY8-6H-Gal2 structure are consistent with the individual ligand binding preferences identified for the alpha/beta and gamma/delta TCRs and thus explain the generation of a carbohydrate-specific T cell response.  (+info)

Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. (3/8493)

Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.  (+info)

Pathogenicity island 2 mutants of Salmonella typhimurium are efficient carriers for heterologous antigens and enable modulation of immune responses. (4/8493)

The potential use as vaccine delivery system of Salmonella typhimurium strains harboring defined mutations in the sseC (HH104) and sseD (MvP101) genes, which encode putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2, was evaluated and compared with that of the well-characterized aroA mutant strain SL7207 by using beta-galactosidase (beta-Gal) as a model antigen. When orally administered to immune-competent or gamma interferon-deficient (IFN-gamma-/-) BALB/c mice, both mutants were found to be highly attenuated (50% lethal dose, >10(9) bacteria). Both strains were also able to efficiently colonize and persist in Peyer's patches. Immunization with HH104 and MvP101 triggered beta-Gal-specific serum and mucosal antibody responses equivalent to or stronger than those observed in SL7207-immunized mice. Although immunoglobulin G2 (IgG2) serum antibodies were dominant in all groups, IgG1 was also significantly increased in mice vaccinated with MvP101 and SL7207. Comparable beta-Gal-specific IgA and IgG antibodies were detected in intestinal lavages from mice immunized with the different strains. Antigen-specific CD4(+) T-helper cells were generated after vaccination with all vaccine prototypes; however, responses were significantly more efficient when HH104 and MvP101 were used (P < 0.05). Significantly higher levels of IFN-gamma were produced by restimulated spleen cells from mice immunized with HH104 than from those vaccinated with the MvP101 or SL7207 derivatives (P +info)

Noncompetitive expansion of cytotoxic T lymphocytes specific for different antigens during bacterial infection. (5/8493)

Listeria monocytogenes is an intracellular bacterium that elicits complex cytotoxic T-lymphocyte (CTL) responses in infected mice. The responses of CTL populations that differ in antigen specificity range in magnitude from large, dominant responses to small, subdominant responses. To test the hypothesis that dominant T-cell responses inhibit subdominant responses, we eliminated the two dominant epitopes of L. monocytogenes by anchor residue mutagenesis and measured the T-cell responses to the remaining subdominant epitopes. Surprisingly, the loss of dominant T-cell responses did not enhance subdominant responses. While mice immunized with bacteria lacking dominant epitopes developed L. monocytogenes-specific immunity, their ability to respond to dominant epitopes upon rechallenge with wild-type bacteria was markedly diminished. Recall responses in mice immunized with wild-type or epitope-deficient L. monocytogenes showed that antigen presentation during recall infection is sufficient for activating memory cells yet insufficient for optimal priming of naive T lymphocytes. Our findings suggest that T-cell priming to different epitopes during L. monocytogenes infection is not competitive. Rather, T-cell populations specific for different antigens but the same pathogen expand independently.  (+info)

Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome. (6/8493)

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.  (+info)

A technique for dual determination of cytotoxic and helper lymphocyte precursor frequency by a miniaturized dye release method. (7/8493)

Helper (HTLPf) and cytotoxic (CTLPf) lymphocyte precursor frequency assays are increasingly used in bone marrow stem cell and organ transplant compatibility testing. Current techniques require large cell numbers and radioisotopes. To improve the technique, we developed a miniaturized fluorescent read-out combined HTLPf/CTLPf limiting dilution assay. The assay requires only 5 x 10(6) stimulators, 2 x 10(6) responders and 0.24 x 10(6) target cells in Terasaki plates (40 microl/well). For the HTLPf, culture supernatants from each well were assayed for IL-2 production. The IL-2-dependent proliferation of the mouse 9.12 cell line was detected by a semi-automated fluorescent dye technique. After addition of rhIL-2 (recombinant human IL-2) on days 3 and 7, CTLPs were detected on day 10 by measuring the lysis of dye-labeled targets. Results were comparable to standard radioisotope-based techniques. The assay had a coefficient of variation of approximately 30%. The assay detected helper CD4 cells, pure cytotoxic CD8, helper CD8 cells and helper/cytotoxic CD8 cells. Discrimination was demonstrated between HLA-matched related and non-related pairs. The ease of testing and small cell numbers required should facilitate further evaluation of HTLPf and CTLPf for compatibility testing in unrelated donor transplantation and monitoring immune responses following adoptive transfer of lymphocytes.  (+info)

Natural variation of the expression of HLA and endogenous antigen modulates CTL recognition in an in vitro melanoma model. (8/8493)

Increasing attention has been devoted to elucidating the mechanism of lost or decreased expression of MHC or melanoma-associated antigens (MAAs), which may lead to tumor escape from immune recognition. Loss of expression of HLA class I or MAA has, as an undisputed consequence, loss of recognition by HLA class I-restricted cytotoxic T cells (CTLs). However, the relevance of down-regulation remains in question in terms of frequency of occurrence. Moreover the functional significance of epitope down-regulation, defining the relationship between MHC/epitope density and CTL interactions, is a matter of controversy, particularly with regard to whether the noted variability of expression of MHC/epitope occurs within a range likely to affect target recognition by CTLs. In this study, bulk metastatic melanoma cell lines originated from 25 HLA-A*0201 patients were analyzed for expression of HLA-A2 and MAAs. HLA-A2 expression was heterogeneous and correlated with lysis by CTLs. Sensitivity to lysis was also independently affected by the amount of ligand available for binding at concentrations of 0.001 to 1 mM. Natural expression of MAA was variable, independent from the expression of HLA-A*0201, and a significant co-factor determining recognition of melanoma targets. Thus, the naturally occurring variation in the expression of MAA and/or HLA documented by our in vitro results modulates recognition of melanoma targets and may (i) partially explain CTL-target interactions in vitro and (ii) elucidate potential mechanisms for progressive escape of tumor cells from immune recognition in vivo.  (+info)

CTLPF - Cytotoxic T-Lymphocyte Precursor Frequency. Looking for abbreviations of CTLPF? It is Cytotoxic T-Lymphocyte Precursor Frequency. Cytotoxic T-Lymphocyte Precursor Frequency listed as CTLPF
TY - JOUR. T1 - Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. AU - Mortarini, Roberta. AU - Borri, Alessandra. AU - Tragni, Gabrina. AU - Bersani, Ilaria. AU - Vegetti, Claudia. AU - Bajetta, Emilio. AU - Pilotti, Silvana. AU - Cerundolo, Vincenzo. AU - Anichini, Andrea. PY - 2000/7/1. Y1 - 2000/7/1. N2 - Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 μg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a ...
Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. ...
TY - JOUR. T1 - Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1- infected long-term survivors. AU - Betts, Michael R.. AU - Krowka, John F.. AU - Kepler, Thomas B.. AU - Davidian, Marie. AU - Christopherson, Cindy. AU - Kwok, Shirley. AU - Louie, Leslie. AU - Eron, Joseph. AU - Sheppard, Haynes. AU - Frelinger, Jeffrey A.. PY - 1999/9/1. Y1 - 1999/9/1. N2 - HIV-1-specific cytotoxic T cell (CTL) activity has been suggested to correlate with protection from progression to AIDS. We have examined the relationship between HIV-specific CTL activity and maintenance of peripheral blood CD4+ T lymphocyte counts and control of viral load in 17 long-term survivors (LTSs) of HIV-1 infection. Longitudinal analysis indicated that the LTS cohort demonstrated a decreased rate of CD4+ T cell loss (18 cells/mm3/year) compared with typical normal progressors (approximately 60 cells/mm3/year). The majority of the LTSs had ...
Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.
Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.
TY - JOUR. T1 - Effector cytotoxic T lymphocyte numbers induced by vaccination should exceed levels in chronic infection for protection from HIV. AU - Altes, H K. AU - Price, D A. AU - Jansen, Vincent A. A.. PY - 2001/10/12. Y1 - 2001/10/12. KW - AIDS Vaccines. KW - CD4-Positive T-Lymphocytes. KW - HIV Infections. KW - Humans. KW - Lymphocyte Count. KW - Models, Immunological. KW - T-Lymphocytes, Cytotoxic. KW - Vaccination. KW - Viremia. M3 - Article. C2 - 11567737. VL - 20. SP - 3. EP - 6. JO - Vaccine. JF - Vaccine. SN - 0264-410X. IS - 1-2. ER - ...
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a transgene driven by the K14 promoter, form a murine model of HPV-mediated epithelial cancers in humans. Our previous studies have shown that K14E7 transgenic skin grafts onto syngeneic mice are not susceptible to immune destruction despite the demonstrated presence of a strong, systemic CTL response directed against the E7 protein. Consistent with this finding, we now show that cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels of E7 protein to a range of CTL-sensitive E7-expressing cell lines but are not susceptible to CTL-mediated lysis in vitro. E7 transgenic and non-transgenic KC are susceptible to conventional mechanisms of CTL-mediated lysis, including perforin and Fas/FasL interaction when an excess of exogenous peptide is provided. The concentration of exogenous peptide required to render a cell susceptible to lysis was similar between KC and other conventional CTL targets (e.g. ...
TY - JOUR. T1 - Rapid and long-term changes to host cytotoxic T lymphocyte precursors reactive to donor antigens caused by intravenous injection of histoincompatible lymphocytes. AU - Martin, Diego R.. AU - Sheng-Tanner, Xiaofang. AU - Miller, Richard G.. PY - 1992/7. Y1 - 1992/7. N2 - It has been shown previously that a single intravenous injection of mouse F, LNC into either parent results in a rapid reduction in the ability of the recipient to generate CTL reactive against donor antigens in an in vitro MLR. The underlying mechanism appears to be the in-activation of host CTL precursors that can recognize donor lymphocytes that have entered the recirculating pool. The donor lymphocytes may be acting as functionally deleting APC, or veto cells. Here, we have injected C57BL/6 (B6) mice with (C57BL/6XDBA/2) F, (FO LNC. The CTL response against donor LNC was maximally reduced by 2 days and stayed reduced for at least 6 weeks, but ultimately recovered to normal levels. The response reduction ...
OBJECTIVE: HIV-specific cytotoxic T lymphocytes (CTL) are believed to play an important role in containing viral replication throughout HIV-1 infection. Previous studies have attempted to quantify the HIV-1-specific CTL precursor frequency during primary HIV infection by using limiting dilution analysis, which almost certainly underestimates the true CTL frequency. Here we use a relatively new technique to quantify HIV-specific CD8 T cells in primary HIV infection. METHODS: We have used soluble tetrameric complexes of HLA class I molecules complexed with HIV epitope peptides to study the dynamics and frequency of HIV-specific CD8 T cells in relation to plasma viral load in early HIV infection, in three patients with a highly focused HIV-specific CTL response. RESULTS: We show that the frequencies of HIV-1-specific CD8 T cells in acute infection are significantly higher than previously documented and can be demonstrated well before full seroconversion. These studies also confirm the immunodominance of
Vaccinia virus (VV) inhibits the presentation of certain epitopes from influenza virus nucleoprotein (NP), haemagglutinin (HA) and non-structural 1 (NS1) proteins to CD8+ cytotoxic T lymphocytes (CTL) by an unknown mechanism. We have investigated whether VV genes B13R and B22R, which encode proteins with amino acid similarity to serine protease inhibitors (serpins), are involved in this process. Recombinant VVs were constructed which express influenza virus proteins HA, NP or NS1 and which lack serpin gene B13R or both B13R and B22R. The lysis of cells infected with these viruses by influenza virus-specific CD8+ CTL was compared to the lysis of cells infected with viruses expressing both the influenza proteins and the serpin genes. Cytotoxicity assays showed that deletion of the VV serpin genes B13R and B22R and other genes between B13R and B24R did not increase the level of lysis, indicating that these genes are not involved in inhibition of antigen presentation of the epitopes tested.
TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ NK cells as well as CD3+CD16- T cells from rIL-2-activated TIL of renal cell carcinoma displayed MHC-nonrestricted cytotoxicity. At the clonal level as ...
The propensity of HIV-1 for genetic variation, a consequence of error-prone reverse transcription combined with high rates of replication, is thought to contribute to the establishment of persistent infection in the host despite the presence of a vigorous antiviral immune response. Protective immunity to viruses is mediated primarily by cytotoxic T lymphocytes, which recognize viral peptides of 8-11 amino acids bound to major histocompatibility complex class I molecules on the surface of infected cells. In this review we examine the mechanisms by which mutation within peptide antigen-encoding regions of the viral genome enables HIV-1 to evade recognition by virus-specific cytotoxic T lymphocytes. The discussion is relevant to other genetically unstable viruses and more generally to intracellular pathogens of variable antigenicity.
|jats:p|The highly sensitive quantitation of virus-specific CD8+ T cells using major histocompatibility complex-peptide tetramer assays has revealed higher levels of cytotoxic T lymphocytes (CTLs) in acute and chronic virus infections than were recognized previously. However, studies in lymphocytic choriomeningitis virus infection have shown that tetramer assays may include measurement of a substantial number of tetramer-binding cells that are functionally inert. Such phenotypically silent CTLs, which lack cytolytic function and do not produce interferon (IFN)-γ, have been hypothesized to explain the persistence of virus in the face of a quantitatively large immune response, particularly when CD4 help is impaired. In this study, we examined the role of functionally inert CTLs in chronic HIV infection. Subjects studied included children and adults (n = 42) whose viral loads ranged from &lt;50 to &gt;100,000 RNA copies/ml plasma. Tetramer assays were compared with three functional assays: enzyme
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The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.
This study demonstrates that use of structural information improves the definition and optimization of cytotoxic T lymphocyte (CTL) epitopes. Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrated that known epitopes varied considerably at anchor positions. We used structural information based on determination of the crystal structure of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structural and immunological data more accurately defines the true peptide-binding motif of a restriction element
Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.
Swine leukocyte antigen (SLA) class I molecules play a crucial role in generating specific cellular immune responses against viruses and other intracellular pathogens. They mainly bind and present antigens of intracellular origin to circulating MHC I-restricted cytotoxic T lymphocytes (CTLs). Binding of an appropriate epitope to an SLA class I molecule is the single most selective event in antigen presentation and the first step in the killing of infected cells by CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA molecules. In this study, we constructed SLA class I complexes in vitro comprising viral epitope peptides, the extracellular region of the SLA-1 molecules, and β2-microglobulin (β2m) using splicing overlap extension polymerase chain reaction (SOE-PCR). The protein complexes were induced and expressed in an Escherichia coli prokaryotic expression system and subsequently purified and refolded. Specific binding of seven SLA-1 proteins to one classical swine fever
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[134 Pages Report] Check for Discount on Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline Review, H2 2017 report by Global Markets Direct. Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen...
The evolution of the HIV-specific CD8+ T cell response in patients receiving potent combination therapy has been well documented in adult patients. However, no study reported whether baseline HIV-specific CD8+ T cell response is linked to treatment outcome. The aims of this study were to investigate both the impact of baseline memory cytotoxic T lymphocytes (CTL) on treatment outcome and the effect of potent therapy on memory HIV-specific CTL in HIV-1-infected pediatric patients. The study group comprised 30 children who started a first-line combination treatment including at least three drugs from two different classes and were longitudinally followed during treatment. Their memory HIV-specific responses were measured at baseline and during treatment, as well as their plasma viremia and CD4+ levels. The intensity of memory Gag-specific CTL and the breadth of the CTL response at the beginning of treatment were significantly correlated with lower plasma viral load during treatment, independently of
The composition of tumor-targeted T cell infiltrates is a major prognostic factor in colorectal cancer (CRC) outcome; however, the functional role of these populations in prolonging patient survival remains unclear. Here, we evaluated 190 patients with CRC for the presence of functionally active tumor-infiltrating lymphocytes (TILs), the tumor specificity of these TILs, and the correlation between patient TILs and long-term survival. Using intracytoplasmic cytokine staining in conjunction with HLA multimers loaded with tumor peptide and antigen-specific cytokine secretion assays, we determined that TNF-α expression delineates a population of tumor antigen-specific (TA-specific) cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-α expression in TILs strongly correlated with an increase in the total amount of intratumoral TNF-α, which is indicative of tumor-specific CTL activity. Moreover, a retrospective multivariate analysis of 102 patients with ...
The composition of tumor-targeted T cell infiltrates is a major prognostic factor in colorectal cancer (CRC) outcome; however, the functional role of these populations in prolonging patient survival remains unclear. Here, we evaluated 190 patients with CRC for the presence of functionally active tumor-infiltrating lymphocytes (TILs), the tumor specificity of these TILs, and the correlation between patient TILs and long-term survival. Using intracytoplasmic cytokine staining in conjunction with HLA multimers loaded with tumor peptide and antigen-specific cytokine secretion assays, we determined that TNF-α expression delineates a population of tumor antigen-specific (TA-specific) cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-α expression in TILs strongly correlated with an increase in the total amount of intratumoral TNF-α, which is indicative of tumor-specific CTL activity. Moreover, a retrospective multivariate analysis of 102 patients with ...
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|jats:p|For viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. When inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (LCMV ARM) induces a CD8(+)-mediated cytotoxic T lymphocyte (CTL) response that clears the infection within 7-14 d (CTL+ [P-]). By contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a CTL response and are thus able to establish a persistent infection in adult mice (CTL- [P+]). This report compares the interaction of CTL+ (P-) and CTL- (P+) viruses with cells of the immune system. Both types of virus initially bind to 2-4% of CD4+ and CD8+ T lymphocytes and replicate within cells of both subsets. The replication of CTL- (P+) and CTL+ (P-) viruses in lymphocytes in vivo is similar for the first 5 d after initiating infection. Thereafter, in mice infected with CTL- (P+) variants, lymphocytes retain viral genetic
Cytotoxic T lymphocytes (CTLs) are generated by immune activation of cytotoxic T cells (Tc cells). They are generally CD8+, which makes them MHC class I restricted. CTLs are able to eliminate most cells in the body since most nucleated cells express class I MHC molecules. The CTL-mediated immune system can be divided into two phases. In the first phase, functional effector CTLs are generated from naive Tc cells through activation and differentiation. In the second phase, affector CTLs destroy target cells by recognizing the antigen-MHC class I complex. In phase one, effector CTLs are generated from CTL precursors. The CTL precursors include naive Tc cells since they are incapable of killing target cells. After a precursor cell has been activated, it can then differentiate into a functional CTL with cytotoxic activity. There are three sequential signals that are required to complete this process. First, there is TCR recognition of the peptide-MHC class I complex. This step allows the cell to ...
Significant data support the hypothesis that HIV-specific cytotoxic T lymphocyte (CTL) responses contribute to the control and potential clearance of the virus. Vaccines designed specifically to induce CTL responses are likely to be well suited for treatment of HIV infection. The conceptual basis of the EP HIV-1090 vaccine is the use of highly defined CTL epitopes as the vaccine immunogen. The vaccine is formulated with a water-soluble polymer that stabilizes and protects the DNA and facilitates uptake by cells. Preclinical studies have shown that the vaccine induces strong CTL responses in animal models. This study will evaluate the safety and tolerability of the vaccine and the immune response to the vaccine in HIV-1-infected individuals who are being treated with highly active antiretroviral therapy (HAART) and have a CD4 count of 350 cells/mm3 or more and fully suppressed viral replication on stable HAART.. Each patient will receive a total of four immunizations to be given at Day 0 and at ...
Because tumor-specific cytotoxic T lymphocytes (CTL) recognize tumor antigen associated with MHC class I molecules expressed on the tumor surface, any alteration in the tumor antigen processing and presentation will greatly affect CTL immunity. In fact, downregulation or complete loss of MHC I molecules have been demonstrated in a wide array of tumors, particularly prostate, colon, lung, and breast cancers (5-12). Disruption or downregulation of antigen processing components, such as TAP (transporters associated with antigen processing) and LMP (components of the proteasome complex) genes have also been observed in several tumor types, including breast, prostate, and renal cancers (13-15). Another tactic tumors exploit is downregulation or alteration of tumor antigens. Several independent research groups described the loss of melanoma-associated antigen either during treatment by adoptive transfer of ex vivo expanded antigen-specific CTL (16) or during immune therapy by tumor vaccinations ...
The role of HIV-specific cytotoxic T-lymphocytes (CTL) in controlling viremia and protecting against disease progression following vertical infection may be dependent upon CTL functional responses as well as on the timing of detection, magnitude, and breadth of the responses. Novel and sensitive assay systems (MHC-peptide tetramers, ELISPOT assays, intracellular cytokine assays) have enhanced the detection and characterization of virus-specific CTL responses in the peripheral blood. This study will use these novel methods to examine the timing of detection, magnitude, specificity, and in vitro functional properties of HIV-specific CTL in infants; to evaluate the effects of potent combination antiretroviral therapy on HIV-specific CTL in infants; and to evaluate the immunogenicity of recombinant pox-based vaccines in HIV infected infants with prolonged viral suppression following early potent combination antiretroviral therapy.. Blood samples from infants born to HIV infected women will be ...
The interaction of T helper (Th) cells with syngeneic and allogeneic cytotoxic T lymphocyte precursors (CTL.P) has been investigated. Unprimed and mixed lymphocyte culture-primed peripheral T cells were used as a source of Th. Thymocytes, which depend upon exogenous Th cells for activation, were used as a source of cytotoxic precursors. Data is presented that demonstrates that at least two pathways of T-T interaction can lead to the activation of cytotoxic lymphocytes. The first is an allogeneic effect, in which Th cells recognize and respond to alloantigens expressed on CTL.P. The second is the interaction of Th cells with syngeneic CTL.P, in which both cell types are thought to respond to alloantigens on stimulator cells. The latter interaction can be shown to be restricted by H-2-linked determinants when primed Th cells are used and allogeneic effects against thymocytes are minimized. Restricted interactions between unprimed Th cells and thymocyte CTL.P have never been observed. Mechanisms ...
PubMed journal article Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antige were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
Cytotoxic T-cell clones were raised in CBA mice that recognised both A/X31 and A/JAP/305/1957 influenza virus. Here, we describe one CTL clone that recognises target cells infected with a recombinant vaccinia virus expressing influenza PB1.
The present study focused on three Gag CTL epitopes restricted by three common HLA alleles in Japanese people (24). The Gag protein is most commonly targeted by CTL-inducing HIV/AIDS vaccines (15). In our endogenous expression system, three A*0201-restricted epitope variants and one B*5101-restricted epitope variant escaped from the wild-type CTL recognition, and four A24-restricted epitope variants escaped from the A24-restricted 3R mutant-reactive CTL recognition. Intriguingly, two A*0201-restricted variants and three A24-restricted variants escaped from CTL killing when the gag clones were expressed endogenously in the target cells by the HIV-1 vector, despite the fact that the synthetic variant peptides were well recognized by the CTLs when loaded onto the MHC class I molecule exogenously. The peptide titration experiments have revealed that the strength of these variant peptides recognition was almost equivalent to that of the A*0201-restricted wild-type peptide or the A24-restricted 3R ...
PURPOSE OF REVIEW: Much of the current HIV-1 vaccine research focuses on harnessing the cytotoxic T-lymphocyte arm of the immune response. However, HIV-1 appears to have an unerring ability to evade cytotoxic T-lymphocyte responses, through the process of escape mutation, and thus the potential benefit of a cytotoxic T-lymphocyte-based vaccine remains uncertain. This review focuses on several recent studies that question whether escape mutation is always detrimental to the host, and may provide new hope for the success of a cytotoxic T-lymphocyte-based vaccine against HIV. RECENT FINDINGS: Several recent studies, in both natural HIV-1 infection and the SIV model, have identified examples of cytotoxic T-lymphocyte escape mutants that revert on transmission to individuals lacking the selecting major histocompatibility complex alleles. The obvious implication of these data is that some cytotoxic T-lymphocyte responses can only be evaded through escape mutations that actually reduce the replicative fitness
Virus-associated hematologic malignancies (EBV lymphoproliferative disease) and opportunistic infections (CMV) represent a major cause of hematopoietic stem cell and solid organ transplantation failure. Adoptive transfer of antigen-specific T lymphocytes appears to be a major and successful immunoth
Townsend, A R. and Skehel, J J., Influenza a specific cytotoxic t-cell clones that do not recognize viral glycoproteins. (1982). Subject Strain Bibliography 1982. 1222 ...
This is a multicenter expanded access protocol to provide human leukocyte antigen (HLA) partially-matched third-party allogeneic EBV-CTLs for the treatment of
Cytotoxic T lymphocyte (CTL) responses have been associated with protection from HIV-1 infection in people with a high degree of exposure to HIV and who show no serological evidence of HIV infection (HEPS, highly exposed persistently seronegative). However, it remains unclear how protective CTL responses could apparently develop in a minority of people, whilst the great majority of HIV-infected people make strong CTL responses yet progress to AIDS and death. In this paper we review the data which supports the hypothesis that the quality of the T-cell response, rather than its magnitude, may be an important factor that merits further investigation.
Previous studies showed an inverse correlation between the plasma viral load (pVL) and the frequency of some HIV-1-specific CTLs in HIV-1-infected individuals, indicating that these CTLs control HIV-1 in vivo (5, 28, 33). However, this correlation was not found in the case of many other HIV-1-specific CTLs (16, 25, 26), suggesting the possibility that the quality of HIV-1-specific CTLs is a critical factor for the control of HIV-1 in vivo. However, it is not easy to assess the quality of HIV-1-specifc CTLs. An assay to directly measure the ability of the CTLs to suppress HIV-1 replication in vitro is a very useful method to evaluate the ability of the CTLs to control HIV-1. A previous study using this assay demonstrated that the ability of HLA-B*5101-restricted HIV-1-specific CTLs to suppress HIV-1 replication is dependent on the epitope recognized by these CTLs (43). In addition, a recent study showed that HLA-A*2402-restricted Nef138-specific CTLs have a strong ability to suppress HIV-1 ...
Jeggo, M H. and Wardley, R C., Generation of cross-reactive cytotoxic t lymphocytes following immunization of mice with various bluetongue virus types. (1982). Subject Strain Bibliography 1982. 3115 ...
TY - JOUR. T1 - Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules. AU - Aldrich, Caria J.. AU - Hammer, Robert E. AU - Jones-Youngblood, Sharon. AU - Koszinowski, Ulrich. AU - Hood, Lee. AU - Stroynowski, Iwona T. AU - Forman D.M.D/Ph.D., James Morse. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 1991. Y1 - 1991. N2 - THE α1 and α2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire1-3. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS (refs 4, 5). CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process6. We previously used a hybrid class I molecule with the α1/α2 domains ...
A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when challenged by related antigens. An important issue is whether costimulatory molecules on the antigen-presenting cells are involved in determining whether T cells will differentiate into effector or memory cells after antigenic stimulation. To address this issue, we have produced mice with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative costimulatory pathways for induction of immunological memory to influenza virus. Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells. Our results demonstrate that the induction of memory T cells and effector T cells can utilize ...
Looking for online definition of T cytotoxic cell in the Medical Dictionary? T cytotoxic cell explanation free. What is T cytotoxic cell? Meaning of T cytotoxic cell medical term. What does T cytotoxic cell mean?
article{628449, abstract = {We describe here a limiting dilution analysis to determine cytotoxic T lymphocyte precursor (CTLp) frequencies against individual HLA-A or -B antigens. This assay is reproducible and showed that the CTLp frequency of an individual remains stable with time. Significant variations in CTLp frequency against the same alloantigen were found in different individuals and even in monozygotic twins, showing that these differences were not (completely) genetically determined. Within an individual, a wide range of CTLp frequencies can be found against different allo-antigens. Serologically cross-reactivity seems not to interfere in this assay. This LDA is a practicable tool for a systematic analysis of CTLp response against selected individual HLA-A or -B antigens and can be used for the selection of HLA mismatched donors for transplantation patients.}, author = {Zhang, Li and Li, Shu Guang and Vandekerckhove, Bart and Termijtelen, Annemarie and Van Rood, Joh J and Claas, Frans ...
Dendritic cells (DC) play a key role in the initiation of T cell-mediated immune responses and may therefore be successfully used in antiviral and antitumor vaccination strategies. Because both strength and duration of an immune response determines the outcome of a vaccination protocol, we evaluated the life span of DC-induced antiviral CTL memory against systemic and peripheral challenge infections with lymphocytic choriomeningitis virus (LCMV). We found that expansion and activation of CTL by DC was transient. Protection against systemic LCMV infection after DC immunization was relatively long-lived (,60 days), whereas complete protection against peripheral infection via intracerebral infection or infection into the footpad with LCMV, where rapid recruitment of effector T cells to the site of infection and elimination of viral pathogen plays a major role, was short-lived (,30 days). Protective immunity was most efficiently restored by administration of antigenic peptides via DC, rather than in ...
Looking for online definition of Cytotoxic T lymphocytes in the Medical Dictionary? Cytotoxic T lymphocytes explanation free. What is Cytotoxic T lymphocytes? Meaning of Cytotoxic T lymphocytes medical term. What does Cytotoxic T lymphocytes mean?
We have previously reported the establishment of cytotoxic T-cell lines from pancreatic cancer patients, by continuously stimulating tumor-draining lymph node cells with allogeneic pancreatic tumor cell lines. After the preliminary characterization of their phenotype and tumor specificity, detailed studies performed with one of the cell lines, W.D., show that it recognizes a specific antigen, a large and heavily glycosylated mucin molecule, expressed on pancreatic and breast tumors and tumor cell lines. Although this recognition appears major histocompatibility complex (MHC)-unrestricted, the antigen receptor used by the cytotoxic T cell is the alpha/beta heterodimer, typically found on MHC-restricted T cells. The target antigen is atypical, however, in its ability to directly bind and activate the T cells in the absence of self MHC, presumably by abundant and regularly repeated antigenic epitopes. These findings are important because they demonstrate a specific T-cell response against a human ...
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Few studies have examined longitudinal changes in human immunodeficiency virus type 1 (HIV)-specific cytotoxic T lymphocytes (CTL). To more closely define the natural history of HIV-specific CTL, we used HLA-peptide tetrameric complexes to study the longitudinal CD8(+) T-cell response evolution in 16 A*0201-positive untreated individuals followed clinically for up to 14 years. As early as 1 to 2 years after seroconversion, we found a significant association between high frequencies of A*0201-restricted p17(Gag/Pol) tetramer-binding cells and slower disease progression (P | 0.01). We observed that responses could remain stable over many months, but any longitudinal changes that occurred were typically accompanied by reciprocal changes in RNA viral load. Phenotypic analysis with markers CD45RO, CD45RA, and CD27 identified distinct subsets of antigen-specific cells and the preferential loss of CD27(+) CD45RO(+) cells during periods of rapid decline in the frequency of tetramer-binding cells. In addition we
Infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6 and E7 is selectively maintained in premalignant and malignant cervical lesions these proteins are attractive candidates for immunotherapeutic and prophylactic strategies. This report describes the construction, characterization and the in vivo immunotherapeutic potential of recombinant Semliki Forest virus (SFV) expressing the HPV16 E6 and E7 proteins (SFV-E6E7). Western blot analysis and immunofluorescence staining demonstrated expression of E6 and E7 in BHK cells infected with SFV-E6E7. Immunization of mice with SFV-E6E7 resulted in an efficient in vivo priming of HPV-specific CTL activity. The induced CTL lysed murine tumor cells transformed with the HPV16 genome and EL4 cells loaded with an
OBJECTIVES: To investigate HLA class I allele frequencies in a Kenyan commercial sex worker (CSW) cohort, and to examine HIV-1 specific cytotoxic T lymphocyte (CTL) responses directed against epitopes derived from locally prevalent clade A virus. METHODS: PCR-single strand polymorphism HLA class I typing. Sequencing of novel alleles and examination of their distribution in the CSW cohort, and a low risk HIV uninfected cohort. The peptide-binding motif of a novel class I allele was predicted, and a panel of candidate CTL epitopes was synthesized whose functional significance was examined using ELISpot and Cr release assays. RESULTS: Class I HLA-A and B frequencies within the cohort are presented. Two novel class I alleles were found, HLA-B*4415 and HLA-Cw*0407. These two class I alleles were relatively common, both in the CSW cohort (2.1% and 3.3% respectively) and in a cohort of lower risk women (1.9% and 3.8% respectively). Allele HLA-B*4415 restricted CTL responses against a novel epitope (EEKAFSPEV)
TY - JOUR. T1 - Erratum. T2 - CD40 ligand-deficient mice generate a normal primary cytotoxic T-lymphocyte response but a defective humoral response to a viral infection (Journal of Virology 70:12 (8379)). AU - Whitmire, J. K.. AU - Slifka, M. K.. AU - Grewal, I. S.. AU - Flavell, R. A.. AU - Ahmed, R.. PY - 1997/1/1. Y1 - 1997/1/1. UR - http://www.scopus.com/inward/record.url?scp=0031033039&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0031033039&partnerID=8YFLogxK. M3 - Comment/debate. AN - SCOPUS:0031033039. VL - 71. JO - Journal of Virology. JF - Journal of Virology. SN - 0022-538X. IS - 2. ER - ...
In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong
Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens. ...
TY - JOUR. T1 - Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte. AU - Nukaya, I.. AU - Yasumoto, M.. AU - Iwasaki, T.. AU - Ideno, M.. AU - Sette, A.. AU - Celis, E.. AU - Takesako, K.. AU - Kato, I.. PY - 1999/1/5. Y1 - 1999/1/5. N2 - Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigen-presenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing ...
Strain AS rats respond with two populations of cytotoxic T lymphocytes to stimulation in vitro by the major histocompatibility complex (MHC)-incompatible strain HL rat tumor (HL-A2T2). One is specific for MHC alloantigens present on both HL-A2T2 and normal HL targets, the other is tumor specific. The activation of these killer cells requires helper T lymphocytes. The tumor-specific helper cells depend on syngeneic radioresistant accessory cells to present the tumor antigens in an immunogenic form. The appropriate helper-accessory cell interaction results in the production of soluble factors which then induce the maturation of precursor cells into effective killer cells. Studies with a procedure for inducing negative selection of T cells in vivo showed that short-term exposure to HL-A2T2 tumor induced selection only for TH but not cytotoxic T lymphocyte precursors (CTLp). Simultaneous injection of supernatants from concanavalin A-activated spleen cell cultures, however, did produce selection of ...
A Phase I-II Trial to Examine the Toxicity of CMV- and EBV- Specific Cytotoxic T Lymphocytes When Used for Prophylaxis Against EBV and CMV Disease in Recipients of CD34-Selected/T Cell-Depleted Stem Cell ...
CD40 expression on human melanoma (MM) was described previously (17 , 18) , but little was known about its biological relevance. Here, we report the functional expression of CD40 on a subset of MM in situ as well as by some MM cell lines in vitro. Specifically, we demonstrate a gradual loss of CD40 expression during melanoma progression in situ. We also found human MM cell lines established from immunogenic MM but not from advanced-stage metastatic tissue positive for the CD40 antigen, thus paralleling the down-regulation of CD40 expression on MM metastases in situ. These results are in line with previous reports that 50% of MM cell lines generated from primary tumors, but only a minority of cell lines derived from metastases express CD40 (18) . In CD40-positive but not in CD40-negative MM, the expression of this antigen was increased after stimulation with IFN-γ or TNF-α but not with IL-1β or CD40L. By FACS analysis, we found none of the MMs positive for CD40L (CD154) using two different ...
We have examined requirements for antigen presentation to a panel of MHC class I-and class II-restricted, influenza virus-specific CTL clones by controlling the form of virus presented on the target cell surface. Both H-2K/D- and I region-restricted CTL recognize target cells exposed to infectious virus, but only the I region-restricted clones efficiently lysed histocompatible target cells pulsed with inactivated virus preparations. The isolated influenza hemagglutinin (HA) polypeptide also could sensitize target cells for recognition by class II-restricted, HA-specific CTL, but not by class I-restricted, HA-specific CTL. Inhibition of nascent viral protein synthesis abrogated the ability of target cells to present viral antigen relevant for class I-restricted CTL recognition. Significantly, presentation for class II-restricted recognition was unaffected in target cells exposed to preparations of either inactivated or infectious virus. This differential sensitivity suggested that these H-2I ...
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein called CD8, which binds to the constant portion of the class I MHC molecule. ...
TY - JOUR. T1 - Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. AU - Kono, Koji. AU - Rongcun, Yang. AU - Charo, Jehad. AU - Ichihara, Fumiko. AU - Celis, Esteban. AU - Sette, Alessandro. AU - Appella, Ettore. AU - Sekikawa, Takayoshi. AU - Matsumoto, Yoshiro. AU - Kiessung, Rolf. PY - 1998. Y1 - 1998. N2 - We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor- associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 +, HER2/neu+ gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines ...
In the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceded by the hemagglutinin leader sequence, we isolated a single base-pair deletion mutant which gave rise to L+NP(1-159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50-58 (the in-frame portion), but also by CTL to epitopes which are downstream of the mutation (366-374 and 378-386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db-restricted epitope 366-374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occurred during polypeptide extension.
Cell-based therapies have intriguing potential for the treatment of a variety of neurological disorders. One such example is genetically engineered cytotoxic T lymphocytes (CTLs) that are being investigated in brain tumor clinical trials. The development of methods for CTL delivery is critical to their use in the laboratory and clinical setting. In our study, we determined whether CTLs can migrate through fibrin matrices and if their migration, survival, and function could be modulated by adding chemokines to the matrix. Our results indicated that CTLs can freely migrate through fibrin matrices. As expected, the addition of the monocyte chemotactic protein-1 (MCP-1), also known as chemokine C-C motif ligand 2 (CCL2), to the surrounding media increased egress of the CTLs out of the fibrin clot. Interleukin (IL) -2 and/or IL-15 embedded in the matrix enhanced T cell survival and further promoted T cell migration. The interleukin-13 receptor alpha 2 specific (IL-13R alpha2) T cells that traveled out of the
Background: Many determinants for a sustained response to lamivudine therapy have been reported but the role of I cell responsiveness remains unclear. The finding that lyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CII) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. Aim: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). Methods: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. Results: After in vitro expansion, sustained responders had more potent CL responses against YMDD, YVDD, and YIDD, as ...
ABSTRACT: Cytotoxic T lymphocytes (CTL) responses are required to fight many diseases such as viral infections and tumors. At the same time, they can cause disease when induced inappropriately. Which factors regulate CTL and decide whether they should remain silent or react is open to debate. The phenomenon called cross-priming has received attention in this respect. That is, CTL expansion occurs if antigen is recognized on the surface of professional antigen presenting cells (APCs). This is in contrast to direct presentation where antigen is seen on the surface of the target cells (e.g. infected cells or tumor cells). Here we introduce a mathematical model, which takes the phenomenon of cross-priming into account. We propose a new mechanism of regulation which is implicit in the dynamics of the CTL: According to the model, the ability of a CTL response to become established depends on the ratio of cross-presentation to direct presentation of the antigen. If this ratio is relatively high, CTL ...
BACKGROUND Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.METHODS We developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation.RESULTS EBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In ...
BACKGROUND Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.METHODS We developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation.RESULTS EBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In ...
In this study, we evaluated the efficacy of human adjuvant vector cells for use as cancer vaccines in dogs and immunodeficient mice using human materials. We used allogeneic human cells, the CD1d-HEK293 cell line loaded α-GalCer and transfected with mRNA-encoding tumor antigen as artificial adjuvant vector cells. Our approach uses antigen-expressing vector cells expressing 2 antigens, which allows for host DC cross-presentation of tumor antigens to naïve T cells while simultaneously presenting iNKT cell ligand to iNKT cells (34, 35). This strategy induces activation of tumor antigen-specific CTLs as well as iNKT cells. An additional benefit of this strategy is the flexibility of mRNA transduction, which uses mRNA derived from tumor cell lines or tumors from third party patients and encodes for tumor antigens without the need for HLA matching. Furthermore, we have found in other studies that transfer of allogeneic cells expressing cell-associated tumor antigen and iNKT cell ligand induces not ...
... adrenaline and cytotoxic lymphocyte function, we re-assessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients ... adrenaline and cytotoxic lymphocyte function, we re-assessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients ... Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule ... Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule ...
Cytotoxic T lymphocyte responses against measles virus.. UytdeHaag FG1, van Binnendijk RS, Kenter MJ, Osterhaus AD. ...
Definition of cytotoxic T-lymphocyte antigen-4. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms ... cytotoxic T-lymphocyte antigen-4. Definition: expressed by activated T cells. When synthesized as a soluble molecule fused to ... because it blocks a costimulatory molecule on B lymphocytes. ...
... produce cytotoxic T lymphocytes. The cytotoxic activity was Theilers-virus specific. It was for the most part mediated by CD8+ ... Theilers virus infection induces a specific cytotoxic T lymphocyte response.. Pena Rossi C1, McAllister A, Fiette L, Brahic M. ... One of the current hypotheses is that demyelination is, at least in part, mediated by virus-specific cytotoxic T lymphocytes ( ... T lymphocytes and H-2 restricted. This is the first demonstration that a specific CTL response is generated during Theilers ...
Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade. Elizabeth Buchbinder and F. Stephen Hodi Department of Medical ... Cytotoxic T-lymphocyte antigen-4 blockade in melanoma. Clin Ther. 2015;37(4):755-763.. View this article via: PubMed CrossRef ... Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key inhibitory receptor that affects T cell function and plays a critical role ... Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity. 2002; ...
Induction of antitumor cytotoxic lymphocytes using engineered human primary blood dendritic cells. Long Wu, Huan Zhang, Yixing ... These cytotoxic lymphocytes suppress lung metastasis of A549/A2.1 lung cancer cells in NSG mice. Both CTLs and NK cells are ... 2 C-F). IL-15, which favors the development of CD8+ cytotoxic lymphocytes, was produced at high levels in both established ... The cytotoxic activity of the ihv-DC-activated lymphocytes was determined by comparing the luciferase activities in the target ...
... recognized by cytotoxic CD8+ T lymphocytes (CTL), was MAGE-A1 which was identified from tumor-infiltrating lymphocytes obtained ... MUC1-Specific Cytotoxic T Lymphocytes in Cancer Therapy: Induction and Challenge. David Roulois,1,2,3 Marc Grégoire,1,2,3 and ... H. Noto, T. Takahashi, Y. Makiguchi, T. Hayashi, Y. Hinoda, and K. Imai, "Cytotoxic T lymphocytes derived from bone marrow ... K. R. Jerome, D. L. Barnd, K. M. Bendt et al., "Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma ...
... Julia Kim, Vandana Gambhir, Attiya Alatery, and ... Vaccines intended to induce a cytotoxic CD8+ T-cell response are highly sought after. However, some of these vaccines can be ...
... cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-α expression in TILs strongly ... Here, we evaluated 190 patients with CRC for the presence of functionally active tumor-infiltrating lymphocytes (TILs), the ...
Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination (CYNTAX). The safety and scientific validity of this study is the ... Combined Infusion of Cytotoxic T-Lymphocytes and Vaccination to Enhance Infection-Specific Immune Reconstitution Post- ... Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks ... To assess the safety and biological efficacy of prophylactically administered donor-derived multi-infection specific cytotoxic ...
... generally requires the participation of CD4+ T-helper lymphocytes, the nature of the help provided to CTLs is unknown. One ... Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) ... T-cell help for cytotoxic T lymphocytes is mediated by CD40- ... Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper ... lymphocytes, the nature of the help provided to CTLs is unknown. One widely held view is that help for CTLs is mediated by ...
Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pip - Market Research Reports and Industry Analysis ... Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Overview. Cytotoxic T ... Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Dormant Products. Cytotoxic ... Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline Review, H1 2018. ...
Cytotoxic T lymphocytes can be separated from other blood cells, grown in the laboratory, and then given to a patient to kill ... A cytotoxic T lymphocyte is a type of white blood cell and a type of lymphocyte. Also called cytotoxic T cell and killer T cell ... cytotoxic T lymphocyte listen (SY-toh-TOK-sik ... LIM-foh-site) A type of immune cell that can kill certain cells, including ... Cytotoxic T lymphocytes can be separated from other blood cells, grown in the laboratory, and then given to a patient to kill ...
Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses: Explanation for the Immunodominance Effect Whereby Cytotoxic T ... The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes. Y Sykulev, R J Cohen, and ... The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes ... The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes ...
Polyclonal activation of human peripheral blood lymphocytes (PBLs) in vitro by preparations of Streptococcus pyogenesSu strain ... Polyclonal activation of human lymphocytes and induction of cytotoxic lymphocytes by streptococcal preparations. ... mediating the following generation of DN cytotoxic effector lymphocytes.. Key words. helper T cells lymphocyte activation ... Two forms of the T cell receptor y protein found on peripheral blood cytotoxic T lymphocytes. Nature 1987; 325: 689-94.PubMed ...
The murine cytotoxic T lymphocyte response to reovirus -- a double-stranded, segmented RNA virus -- has been analyzed using the ... Cytotoxic T lymphocyte recognition of class I H-2 antigens after DNA-mediated gene transfer. Fed. Proc. 43: 271-275, 1984PubMed ... Cytotoxic T lymphocytes recognize determinants on the BALB/c-H- 2Ld molecule controlled by al and a2 but not a3 external ... The murine cytotoxic T lymphocyte response to reovirus -- a double-stranded, segmented RNA virus -- has been analyzed using the ...
Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus, ... Radial Mobility and Cytotoxic Function of Retroviral Replicating Vector Transduced, Non-adherent Alloresponsive T Lymphocytes ... Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes, An Endothelial Planar Cell Model for Imaging ... Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells by Comparing the Cr51 Release Assay to the ...
Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection.. OConnor DH1, Allen TM, ... Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. Despite two reports of CTL- ...
Allogeneic CMV/AdV-specific cytotoxic T lymphocytes are prepared by exposing donor-derived CTLs to a lethally irradiated ... A population of allogeneic cytotoxic T lymphocytes (CTLs) specifically reactive to cytomegalovirus (CMV) and adenovirus (AdV) ... allogeneic CMV/AdV-specific cytotoxic T lymphocytes A population of allogeneic cytotoxic T lymphocytes (CTLs) specifically ... Allogeneic CMV/AdV-specific cytotoxic T lymphocytes are prepared by exposing donor-derived CTLs to a lethally irradiated ...
Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes (VIRAGE). The safety and scientific validity of ... cytotoxic T Lymphocytes. CMV. Adenovirus Infection. viral infection. hematopoietic stem cell transplantation. ... Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes for the Prophylaxis and Treatment of EBV, CMV, ... Available multi-virus-specific cytotoxic T lymphocytes. *Negative pregnancy test in female patients if applicable (childbearing ...
Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) (CHALLAH). The safety and scientific validity ... Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL). Official Title ICMJE Most Closely HLA Matched ... Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation Or Infection With Adenovirus, CMV and ... EBV-LCLs are derived from PBMC-B lymphocytes by infection with a clinical grade, laboratory strain of Epstein-Barr virus (EBV ...
These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host ( ... Cytotoxic" by people in Harvard Catalyst Profiles by year, and whether "T-Lymphocytes, Cytotoxic" was a major or minor topic of ... "T-Lymphocytes, Cytotoxic" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes. Clin Cancer Res. 2019 04 ...
... virus at the epithelium level by modeling and analyzing the interaction of the influenza virus specific cytotoxic T Lymphocytes ... Keywords: cytotoxic T lymphocytes, immune response, influenza virus, mathematical model.. Mathematics Subject Classification: ... Modeling the interaction of cytotoxic T lymphocytes and influenza virus infected epithelial cells. Abdessamad Tridane 1, and ... Modeling the interaction of cytotoxic T lymphocytes and influenza virus infected epithelial cells. Mathematical Biosciences & ...
Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline Review, H2 2017 Summary Cytotoxic T... ... 29, 2017 /PRNewswire/ -- Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - ... Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - CTLA4 also known as CD152 is ... Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - Pipeline Review, H2 2017 ...
3rd Party LMP1/2-Specific Cytotoxic T Lymphocytes for EBV-Associated Lymphoma. The safety and scientific validity of this study ... A Multicenter Pilot Study of Third Party LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Refractory / ... 3rd Party LMP1/2-Specific Cytotoxic T Lymphocytes for EBV-Associated Lymphoma ...
A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering ... A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma. Br J ... Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders ... Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic ...
Murine CD8+ cytotoxic T lymphocytes lyse Toxoplasma gondii-infected cells.. C S Subauste, A H Koniaris and J S Remington ... Murine CD8+ cytotoxic T lymphocytes lyse Toxoplasma gondii-infected cells. Message Subject (Your Name) has forwarded a page to ... This cytotoxic activity was genetically restricted. Spleen cells from T. gondii-immune BALB/c mice were not cytotoxic for T. ... gondii were cytotoxic for T. gondii-infected P815 (H-2d) mastocytoma cells but not for uninfected cells. This cytotoxic ...
Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type 16 E7-derived peptide J Gen Virol 1997 78: ... Induction of cytotoxic T lymphocytes specific for a syngeneic tumor expressing the E6 oncoprotein of human papillomavirus type ... Cytotoxic T lymphocytes raised against a subdominant epitope offered as a synthetic peptide eradicate human papillomavirus type ... Daemen, T., Pries, F., Bungener, L. et al. Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte ...
Cytotoxic T-Lymphocyte-Associated Antigen-4 Message Subject (Your Name) has forwarded a page to you from Clinical Cancer ... Cytotoxic T-Lymphocyte-Associated Antigen-4. April KS Salama and F. Stephen Hodi ... Regulatory checkpoints, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), serve to attenuate this signal, thereby ...
The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong ... Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS Nat Med. 1997 Feb;3(2): ... The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong ...
  • The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs). (pnas.org)
  • Both CTLs and NK cells are found to infiltrate lung as well as lymphoid tissues, mimicking the in vivo trafficking patterns of cytotoxic lymphocytes. (pnas.org)
  • To assess the safety and biological efficacy of prophylactically administered donor-derived multi-infection specific cytotoxic T lymphocytes (CTLs) (targeting cytomegalovirus (CMV), Adenovirus (Adv), Epstein Barr virus (EBV), Varicella-Zoster virus (VZV), Influenza (Flu), BK virus (BKV), and Aspergillus (Asp)) combined with early immunisation with Influenza and VZV vaccines for the prevention of viral and fungal infection following allogeneic blood or marrow stem cell transplantation. (clinicaltrials.gov)
  • Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper lymphocytes, the nature of the 'help' provided to CTLs is unknown. (nih.gov)
  • CD8 + cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. (jci.org)
  • A population of allogeneic cytotoxic T lymphocytes (CTLs) specifically reactive to cytomegalovirus (CMV) and adenovirus (AdV) with potential antiviral activity. (cancer.gov)
  • Allogeneic CMV/AdV-specific cytotoxic T lymphocytes are prepared by exposing donor-derived CTLs to a lethally irradiated Epstein-Barr virus-positive lymphoblastoid B cell line (EBV-LCL) that has been transduced with a clinical-grade adenoviral vector (Ad5f35CMVpp65) as a source of CMV and AdV antigens. (cancer.gov)
  • Cytotoxic T lymphocytes (CTLs) recognize foreign antigens, including viral proteins, in association with major histocompatibility complex (MHC) class I molecules. (sciencemag.org)
  • Memory and distribution of virus-specific cytotoxic T lymphocytes (CTLs) and CTL precursors after rotavirus infection. (thefreedictionary.com)
  • That publication, as well as subsequent research, demonstrated that the RNA encoding the catalytic reverse transcriptase protein component of human telomerase (hTERT RNA), when introduced into dendritic cells, can stimulate the immune system to produce cytotoxic T lymphocytes (CTLs, or killer-T cells) capable of recognizing and destroying telomerase-positive cancer cells. (thefreedictionary.com)
  • Upon immunization, the TERT RNA-modified dendritic cells educate specialized killer cells known as cytotoxic T lymphocytes (CTLs) to recognize and destroy cancer cells expressing telomerase. (thefreedictionary.com)
  • AIMS/BACKGROUND: To determine the functional properties and cytokine production profiles of melanoma specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood leucocytes of two patients with Vogt-Koyanagi-Harada disease (VKH). (bmj.com)
  • RESULTS: CTLs showed strong cytotoxic activity against P-36. (bmj.com)
  • The finding that lyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CII) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. (ebscohost.com)
  • Cytotoxic T lymphocytes (CTLs) that infiltrate the heart are important immune effectors implicated in heart transplant rejection, myocarditis, and other cardiomyopathies. (ovid.com)
  • The cytotoxic activities of CTLs against tumor cells in monolayer culture and tumor spheroids formed in U-bottom 96-well culture plates were assessed. (springer.com)
  • In this paper we explore viral strain dynamics by developing a mathematical model that includes a simple viral life cycle, the effects of periodic treatment (including interruptions) and an immune system response in the form of cytotoxic T-lymphocytes (CTLs). (scielo.org.za)
  • These observations permit the development of new T-cell vaccine strategies capable of inducing an MUC1-specific cytotoxic T cell response in cancer patients. (hindawi.com)
  • The aim of this work is to investigate the mechanisms involved in the clearance of viral infection of the influenza virus at the epithelium level by modeling and analyzing the interaction of the influenza virus specific cytotoxic T Lymphocytes (CTL cells) and the influenza virus infected epithelial cells. (aimsciences.org)
  • Antigen-specific cytotoxic T cells can be generated by primary in vitro stimulation of spleen cells from C57BL/6 mice with appropriate peptide fragments. (rupress.org)
  • Dendritic cells (DCs) pulsed with HBsAg efficiently reverse the immune tolerance to hepatitis B virus (HBV) and induce HBV-specific cytotoxic T lymphocyte (CTL) responses in transgenic mice and healthy volunteers. (wiley.com)
  • Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and children. (thefreedictionary.com)
  • The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. (nih.gov)
  • Enhancements in the cytotoxic activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment are crucial for the development of cancer immunotherapy. (springer.com)
  • The total number, type, and activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment need to be clarified, particularly for the development of companion diagnostics to identify patients for whom these therapies are effective. (springer.com)
  • The efficacy of glioma-specific cytotoxic T-lymphocyte for a syngeneic murine malignant glioma (a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma) was investigated. (acronymattic.com)
  • Show abstract] [Hide abstract] ABSTRACT: The effects of interleukin 2 (IL2) and interferon (IFN) on the generation and lytic activation of syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203- glioma)-specific cytotoxic T-lymphocyte (G-CTL) were investigated. (acronymattic.com)
  • The present study is a report of a novel approach of targeting malignant glioma with IL-13Ra2-specific cytotoxic T lymphocyte . (acronymattic.com)
  • Through frequent sample time points, we used HLA-peptide tetrameric complexes to characterize the detailed kinetics of the human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) response after potent antiretroviral therapy in eight treated individuals. (asm.org)
  • Immune effectors, such as HIV-specific cytotoxic T-lymphocytes (CTL) , is needed to recognize and eliminate these cells with exposed targets. (selleckchem.com)
  • Thus, the development of assay systems, which optimize cell usage, while still allowing for the detailed determination of breadth and magnitude of virus-specific cytotoxic T lymphocyte (CTL) responses, is urgently needed. (harvard.edu)
  • The objective of this study was to characterize the phenotype(s) of the effector cell population responsible for HPV-16 E6- and E7-specific cytotoxic responses. (asm.org)
  • We have previously reported that cord blood T cells can give rise to allo-specific cytotoxic T lymphocyte (CTL) just like adult T cells. (nii.ac.jp)
  • Cytotoxic T lymphocyte responses against measles virus. (nih.gov)
  • Responses observed with such immune checkpoint therapy can follow a different pattern from that seen with cytotoxic chemotherapy or targeted therapy and may continue after therapy is discontinued. (jci.org)
  • Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. (nih.gov)
  • Responses such as T cell proliferation (replication of white blood cells in laboratory tests), the production of interferon (produced by lymphocytes in response to a viral infection) and the production of cytotoxic T lymphocytes (killer T cells) were induced by the vaccine. (thefreedictionary.com)
  • Yunhan Jiang, "Characterization of Memory Cytotoxic T Lymphocyte Responses. (pitt.edu)
  • Mutations in HIV epitopes recognized by cytotoxic T lymphocytes (CTL) could be a major contributing factor because they result in T cell mediated immune responses with limited effectiveness. (pitt.edu)
  • Ganesan AP et al (2017) Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. (springer.com)
  • Among mechanisms responsible for tumor immune escape, great relevance is attributed to tumor infiltration by regulatory T lymphocytes (Treg), 3 based on the observation that these cells are present in tumor-infiltrating lymphocytes (TILs), inhibit antitumor immune responses and their rate of infiltration correlates with tumor progression ( 5 ). (jimmunol.org)
  • We use simple mathematical models to examine the dynamics of primary and secondary cytotoxic T-lymphocyte (CTL) responses to viral infections. (royalsocietypublishing.org)
  • Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory receptor expressed by T lymphocytes that acts largely as a negative regulator of T-cell responses ( 28 ). (asm.org)
  • Cytotoxic T-lymphocyte (CTL) responses to E6 and E7 were previously shown to be more commonly detectable in human papillomavirus type 16 (HPV-16)-positive women without squamous intraepithelial neoplasia (SIL) than in HPV-16-positive women with SIL (M. Nakagawa, D. P. Stites, S. Farhat, J. R. Sisler, B. Moss, F. Kong, A. B. Moscicki, and J. M. Palefsky, J. Infect. (asm.org)
  • Our results suggest that both CD4 and CD8 T lymphocytes contribute to HPV-16 E6- and E7-specific CTL responses although their relative contributions vary from individual to individual. (asm.org)
  • In a previous study ( 13 ), we showed that cytotoxic T-lymphocyte (CTL) responses to HPV type 16 (HPV-16) E6 and E7 proteins appear to be important in the prevention of SIL in that responses to both E6 and E7 proteins were more commonly found in HPV-16-positive women without SIL than in HPV-16-positive women with SIL. (asm.org)
  • Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. (frontiersin.org)
  • In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. (frontiersin.org)
  • Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or nicotine showed normal 51Cr release and their viability was comparable to that of untreated control cells. (nih.gov)
  • C-dependent cytolysis and cell sorting experiments of OK-432-activated LBCs revealed that both CD3 + and CD3 − types of CD4 − CD8 − DN lymphocytes, but not CD4 + helper T cells, may be major populations responsible for the cytotoxicity induced. (springer.com)
  • The effector cells were shown to be CD8+ T lymphocytes, because the cytotoxicity was significantly inhibited by depletion of CD8+ T lymphocytes but not by depletion of CD4+ T lymphocytes. (jimmunol.org)
  • Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset, fatal disease characterized by a sepsislike illness with cytopenia, hepatosplenomegaly, and deficient lymphocyte cytotoxicity. (bloodjournal.org)
  • CD8 + T cells differentiate to cytotoxic T cells, traffic into the tumor microenvironment, and exhibit cytotoxicity against tumor cells. (springer.com)
  • 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. (jimmunol.org)
  • Functional assay of cytotoxic lymphocytes involved in antibody-mediated cytotoxicity in normal and rheumatoid subjects. (bmj.com)
  • Antibody-mediated lymphocyte-induced cytotoxicity (K cell activity) was measured in a system consisting of Chang human liver cells, rabbit anti-Chang antiserum, and Triosil-Ficoll purified human lymphocytes. (bmj.com)
  • At the same time, a mixed lymphocyte culture was set as a positive cytotoxicity control with an irradiated (40 Gy) allogeneic Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line (LCL) (10 6 cells/well) for stimulation. (asm.org)
  • The discovery that a unique type of lymphocyte was responsible for "natural" or spontaneous cytotoxicity was made in the early 1970s by doctoral student Rolf Kiessling and postdoctoral fellow Hugh Pross, in the mouse, and by Hugh Pross and doctoral student Mikael Jondal in the human. (wikipedia.org)
  • The in vitro effects of the recreational drugs, ethanol (EtOH) and nicotine, on natural killer (NK) antibody-dependent cellular cytotoxic (ADCC) and lymphokine-activated killer (LAK) cell activities on normal lymphocytes were investigated. (nih.gov)
  • Polyclonal activation of human peripheral blood lymphocytes (PBLs) in vitro by preparations of Streptococcus pyogenes Su strain (OK-432) and other heat-killed strains was investigated. (springer.com)
  • These results suggest that the OK-432 and other streptococcal preparations stimulate the human PBLs in vitro to induce the proliferation/activation of CD4 + T cells, mediating the following generation of DN cytotoxic effector lymphocytes. (springer.com)
  • 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. (harvard.edu)
  • This cytotoxic activity was remarkably increased after in vitro stimulation with T. gondii-infected syngeneic spleen cells. (jimmunol.org)
  • Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. (rupress.org)
  • The primary in vitro cytotoxic T cell response was peptide specific, since targets were lysed only in the presence of appropriate peptide antigens. (rupress.org)
  • However, cytotoxic T cell lines generated in vitro against the NP365-380 peptide did contain a minor population of virus-reactive cells that could be selectively expanded by stimulation with A/PR/8-infected spleen cells. (rupress.org)
  • The aim of this study was, therefore, to investigate the influence of LEV and VPA on apoptosis and cytotoxic function of CD8+ T lymphocytes in vitro. (uni-marburg.de)
  • Methods: After isolation of peripheral blood mononuclear cells (PBMCs) in 15 healthy subjects (9 female (60%), age: 35.7±12.1 years), apoptosis and cytotoxic function of CD8+ T lymphocytes were measured in vitro using immunofluorescence labeling and flow cytometry. (uni-marburg.de)
  • Expression of the fluorescent fusion protein allows quantitative analyses of cytotoxic granule maturation, transport and fusion in vitro with super-resolution imaging techniques, and two-photon microscopy in living knock-ins enables the visualization of tissue rejection through individual target cell-killing events in vivo. (elifesciences.org)
  • We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. (asm.org)
  • To study T cells in vivo, we developed a new knock-in mouse line, which expresses a fusion protein of granzyme B, a key component of cytotoxic granules involved in T cell-mediated target cell-killing, and monomeric teal fluorescent protein from the endogenous Gzmb locus. (elifesciences.org)
  • Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. (frontiersin.org)
  • Pretreatment of target cells with either EtOH or nicotine for 4 hr did not affect cytotoxic activity. (nih.gov)
  • Further, the DC-activated cytotoxic T lymphocytes and NK cells potently suppress tumor growth and metastasis in human lung cancer mouse models. (pnas.org)
  • These cytotoxic lymphocytes suppress lung metastasis of A549/A2.1 lung cancer cells in NSG mice. (pnas.org)
  • Among professional antigen-presenting cells, dendritic cells (DCs) hold unique abilities to prime naïve T lymphocytes in mediating antigen-specific, adaptive immune response ( 1 ). (pnas.org)
  • The proliferative response is accompanied by the generation of lymphoblastic cells (LBCs), which consist of heterologous lymphocyte populations: CD4 + helper type of T cells, and CD4 − CD8 − double-negative (DN) lymphocytes, including both CD3 + TcR γδ + T cells and CD2 + CD3 − immature type of T or non-T cell type of lymphocytes. (springer.com)
  • Almost all the LBCs express Leu19, TfR (transferrin receptor), LFA-1 and CD38 (OKT10) antigens, which are expressed on activated T cells, NK cells and some other lymphocytes. (springer.com)
  • On the other hand, CD4 − CD8 T cells may be required for the proliferation of PBLs and generation of cytotoxic effector cells. (springer.com)
  • Blanden, R. V., Dunlop, M. B. C., Doherty, P. C., and Kohn, H. I.: Effects of four H-2K mutations on virus-induced antigens recognized by cytotoxic T cells. (springer.com)
  • Immunized T-lymphocytes which can directly destroy appropriate target cells. (jove.com)
  • Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) - CTLA4 also known as CD152 is a protein receptor found on the surface of T cells. (bharatbook.com)
  • Investigators want to see if a kind of white blood cell called T lymphocytes (T cells)can be used to prevent and treat adenovirus, CMV and EBV in the early stages of reactivation or infection. (clinicaltrials.gov)
  • The APCs used to stimulate and expand the CMV-specific T cells will be derived from patient mononuclear cells and B lymphocytes. (clinicaltrials.gov)
  • Cytotoxic T lymphocytes can be separated from other blood cells, grown in the laboratory, and then given to a patient to kill cancer cells. (cancer.gov)
  • Murine CD8+ cytotoxic T lymphocytes lyse Toxoplasma gondii-infected cells. (jimmunol.org)
  • Studies were performed to determine whether CTL against Toxoplasma gondii-infected cells could be induced in a murine model of T. gondii infection in which CD8+ T lymphocytes have been shown to play a major role in resistance against this parasite. (jimmunol.org)
  • In 51Cr release assays, nylon wool nonadherent spleen cells from BALB/c (H-2d) mice immunized with the temperature-sensitive (ts-4) mutant strain of T. gondii were cytotoxic for T. gondii-infected P815 (H-2d) mastocytoma cells but not for uninfected cells. (jimmunol.org)
  • Spleen cells from T. gondii-immune BALB/c mice were not cytotoxic for T. gondii-infected EL4 (H-2b) thymoma cells, whereas spleen cells from T. gondii-immune C57B1/6 (H-2b) mice were cytotoxic for T. gondii-infected EL4 cells but not for T. gondii-infected P815 cells. (jimmunol.org)
  • The cytolytic activity of CD8+ T lymphocytes against T. gondii-infected cells might be a mechanism whereby these cells confer resistance against T. gondii. (jimmunol.org)
  • Cytotoxic T lymphocytes (CTL) kill virally infected and tumourigenic cells via the regulated secretion of specialised secretory lysosomes. (bl.uk)
  • are studying the action of cytotoxic T lymphocytes , cellular immune responders that attack foreign or infected cells. (thefreedictionary.com)
  • Data in murine models show that cytotoxic T lymphocytes (CTL) can kill malignant cells that express WT1 with a high degree of safety. (thefreedictionary.com)
  • The article, entitled "Dendritic Cells Transduced with Full-Length Wild-Type p53 Generate Antitumor Cytotoxic T Lymphocytes from Peripheral Blood of Cancer Patients," indicated that dendritic cells treated with INGN 201 were able to induce a specific antitumor immune response mediated by cytotoxic T lymphocytes , or killer T cells. (thefreedictionary.com)
  • Is the Subject Area "Cytotoxic T cells" applicable to this article? (plos.org)
  • Taken together, these observations provide evidence that specific cellular immunity to reovirus in IEL is mediated at least in part, by conventional cytotoxic T lymphocytes and that these cells are functionally and phenotypically similar to the pCTL derived from the Peyer's patches. (unboundmedicine.com)
  • Thus, lymphocytes scan the environment for information from other cells as their input and vice versa . (frontiersin.org)
  • The serine-threonine kinase mammalian target of rapamycin (mTOR) is an important integrator of nutrient, cytokine and growth factor sensing in T cells and controls transcriptional programs that determine CD8+ cytotoxic T cell fate and trafficking. (bl.uk)
  • The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. (medworm.com)
  • Purified cytoplasmic granules from cytotoxic rat large granular lymphocytes (LGL) tumors were cytolytic to erythrocytes, splenocytes, and a number of different lymphoid tumor cells. (rupress.org)
  • In contrast to cancer vaccines, CAR T cells, and BiTEs, immune checkpoint inhibitors enhance the activity of cytotoxic T cells by inhibiting the negative regulators of T cells. (springer.com)
  • Cepek KL et al (1994) Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. (springer.com)
  • CD4 + CD25 + T regulatory lymphocytes associate with CD8 + CD28 − T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. (jimmunol.org)
  • Complementary transcripts were detected in cytotoxic T lymphocytes, spleen cells from nude mice, a rat natural killer cell leukemia, and in two of eight T-helper clones (both cytotoxic), but not in normal mouse kidney, liver, spleen, or thymus, nor in several tested T- and B-cell tumors. (sciencemag.org)
  • Developmentally, T stem cells were able to self-renew and both give rise to abundant cytotoxic effector CD8+ T cells in the presence of antigen as well as contribute to the pool of long-term central memory CD8+ T cells following antigen clearance. (upenn.edu)
  • The antitumor activities of cytolytic T lymphocytes and natural killer cells are being increasingly investigated and exploited in cancer immunotherapy. (ascopost.com)
  • One mechanism by which these cells recognize tumor cells is by engagement of NKG2D, an activating receptor on cytolytic T lymphocytes and natural killer cells, by MICA/B and ULBP family stress antigens. (ascopost.com)
  • The immune system has opposing roles in tumorigenesis: It can promote tumor development, via an inflammatory response, or suppress tumor development, via the continuous elimination of nascent tumor cells by antigen-specific lymphocytes in a process known as cancer immunosurveillance. (aacrjournals.org)
  • Flow cytometric and gene expression analyses revealed the presence of two novel lineages of Gzmb-expressing lymphocytes in transformed tissues: unconventional type 1 innate lymphoid cells (ILC1I) and type 1 innate-like T cells (ILTC1), both of which were functionally similar to, but transcriptionally distinct from, conventional NK (cNK) cells. (aacrjournals.org)
  • Together, these results show that oncogenic transformation provokes the expansion of lineages of unconventional tissue-resident cytotoxic lymphocytes, but not cNK cells, to drive cancer immunosurveillance. (aacrjournals.org)
  • The possible use of innate effector lymphocytes, including natural killer (NK) cells, NKT cells and γ δ T cells, for tumor immunotherapy is of recent interest. (haematologica.org)
  • T-cell receptor γ δ T cells constitute an important subset of cytotoxic non-conventional effectors involved in immune reactions against mycobacteria and tumors. (haematologica.org)
  • CD8+ cytotoxic T lymphocyte (CTL) can recognize and kill target cells that express only a few cognate major histocompatibility complex class I-peptide (pMHC) complexes. (epfl.ch)
  • Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. (asm.org)
  • Studies aimed at elucidating the mechanism of action of 1D11 in mice lacking specific immune effector cells suggest that the activity of cytotoxic T lymphocytes is important in the inhibition of metastases. (aacrjournals.org)
  • Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells. (asm.org)
  • Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blood mononuclear cells). (asm.org)
  • Cytotoxic, or killer, T cells are a key part of the immune system. (elifesciences.org)
  • Tagging a protein inside the cytotoxic granules would allow close monitoring of T cells as they encounter, recognize and kill their targets. (elifesciences.org)
  • Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2α) has been discovered and expressed in mouse activated T-cells and mast cells. (ajol.info)
  • The objective of this study was to determine whether the HPV-specific effectors responsible for the CTL response were primarily CD4 T lymphocytes and whether natural killer (NK) cells contributed to the observed killing. (asm.org)
  • d ) Sorting strategy of naive and cytotoxic T cells according to expression of CD45RO, CD28 and CD27. (elifesciences.org)
  • The expression of CD8α and CD8β subunits by naive and cytotoxic CD4 and CD8 T cells was measured by flow cytometry. (elifesciences.org)
  • Publications] Umemoto M, Azuma E,: 'Two cytotoxic pathways of natural killer cells in human cord blood : implications in cord blood transplantation. (nii.ac.jp)
  • Jakmip1 is absent in naive CD8(+) and CD4(+) T lymphocytes from peripheral blood but is highly expressed in Ag-experienced T cells. (pasteur.fr)
  • Simian virus 40 (SV40) tumor (T) antigen expressed in H-2b SV40-transformed cells induces the generation of Lyt-2+ (CD8+) cytotoxic T lymphocytes (CTL), which are involved in tumor rejection, in syngeneic mice. (eurekamag.com)
  • A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways. (wikipedia.org)
  • Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. (wikipedia.org)
  • CD8+ T cells are recognized as TC cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system. (wikipedia.org)
  • It is the CD8+ T-cells that will mature and go on to become cytotoxic T cells following their activation with a class I-restricted antigen. (wikipedia.org)
  • The activation of cytotoxic T cells is dependent on several simultaneous interactions between molecules expressed on the surface of the T cell and molecules on the surface of the antigen-presenting cell (APC). (wikipedia.org)
  • Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of innate lymphoid cells (ILC) and represent 5-20% of all circulating lymphocytes in humans. (wikipedia.org)
  • The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. (wikipedia.org)
  • This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells. (wikipedia.org)
  • NK cells (belonging to the group of innate lymphoid cells) are one of the three kinds of cells differentiated from the common lymphoid progenitor, the other two being B and T lymphocytes. (wikipedia.org)
  • Kiessling's research involved the well-characterized ability of T lymphocytes to lyse tumor cells against which they had been previously immunized. (wikipedia.org)
  • The murine cytotoxic T lymphocyte response to reovirus -- a double-stranded, segmented RNA virus -- has been analyzed using the dm1 mutant and its d parent strain. (springer.com)
  • A new serine protease was encoded by a clone isolated from a murine cytotoxic T-lymphocyte complementary DNA library by an RNA-hybridization competition protocol. (sciencemag.org)
  • To define the specific immune response elicited by oncogene-induced cancers, Dadi and colleagues characterized cytotoxic lymphocytes in transgenic models of murine mammary and prostate cancers. (aacrjournals.org)
  • Cytotoxic T lymphocyte (CTL) epitopes within the HCV non-structural proteins were identified, and proteasomal cleavage sites and helper T cell (Th) epitopes at close proximity to these CTL epitopes were analyzed using multiple prediction algorithms. (mdpi.com)
  • Ip PP, Nijman HW, Daemen T. Epitope Prediction Assays Combined with Validation Assays Strongly Narrows down Putative Cytotoxic T Lymphocyte Epitopes. (mdpi.com)
  • Thus, the new mouse line is an ideal tool to study cytotoxic T lymphocyte biology and to optimize personalized immunotherapy in cancer treatment. (elifesciences.org)
  • Adoptive immunotherapy with human cytotoxic T lymphocytes (CTL) is a promising cancer treatment. (springer.com)
  • Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. (frontiersin.org)
  • A repertoire of membrane receptors along with a milieu of intracellular secretory molecules provide input signals to drive various transcriptional master regulators that commit lymphocyte subsets to send a certain array of outputs. (frontiersin.org)
  • Lymphocyte subsets and ocular inflammation: future prospects for immune deviation therapy? (bmj.com)
  • T-cell lines obtained by the method reporter here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii. (asm.org)
  • Naive and cytotoxic T cell subsets were gated using the markers and strategy illustrated in Figure 1d . (elifesciences.org)
  • We have studied the expression of Jakmip1 mRNA and protein in distinct subsets of human primary lymphocytes. (pasteur.fr)
  • Liu SQ, Saijo K, Todoroki K and Ohno T (1995) Induction of human autologous cytotoxic T lymphocytes on formalin-fixed and paraffin-embedded tumor sections. (springer.com)
  • Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) pipeline Target constitutes close to 43 molecules. (bharatbook.com)
  • The latest report Cytotoxic T Lymphocyte Protein 4 - Pipeline Review, H1 2018, outlays comprehensive information on the Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (bharatbook.com)
  • It also reviews key players involved in Cytotoxic T Lymphocyte Protein 4 (Cytotoxic T Lymphocyte Associated Antigen 4 or CD152 or CTLA4) targeted therapeutics development with respective active and dormant or discontinued projects. (bharatbook.com)
  • The global Cytotoxic T Lymphocyte Protein 4 market is valued at XX million USD in 2016 and is expected to reach XX million USD by the end of 2022, growing at a CAGR of XX% between 2016 and 2022. (reportsnreports.com)
  • This report studies the Cytotoxic T Lymphocyte Protein 4 development status and future trend in China, focuses on top players in China, also splits Cytotoxic T Lymphocyte Protein 4 by type and by applications, to fully and deeply research and reveal the market general situation and future forecast. (reportsnreports.com)
  • Therapies that target cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have provided unprecedented clinical benefits in various types of cancer. (aacrjournals.org)
  • Publications] Umemoto M, Azuma E,: 'Cytokine-enhanced mixed lymphocyte reaction(MLR) in cord blood. (nii.ac.jp)
  • EtOH also inhibited the activities of Percoll-separated, NK-enriched large granular lymphocytes. (nih.gov)
  • Compensatory mutations restore the replication defects caused by cytotoxic T lymphocyte escape mutations in hepatitis C virus polymerase. (harvard.edu)
  • A cytotoxic T lymphocyte is a type of white blood cell and a type of lymphocyte. (cancer.gov)
  • Vaccines intended to induce a cytotoxic CD8+ T-cell response are highly sought after. (hindawi.com)
  • Räsänen L, Karhumäki E, Marjuri R, Arvilommi H. Bacteria induce lymphokine synthesis polyclonally in human B lymphocytes. (springer.com)
  • Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. (frontiersin.org)
  • The ring junction contained lymphocyte function associated antigen-1 and talin, but did not trigger polarization and granule translocation to the interface. (washington.edu)
  • Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions. (wellnessresources.com)
  • EtOH-induced inhibition of NK activity could be reversed by incubating lymphocytes for 1 hr with interferon. (nih.gov)
  • AU - Cuff,C F, AU - Cebra,C K, AU - Rubin,D H, AU - Cebra,J J, PY - 1993/6/1/pubmed PY - 1993/6/1/medline PY - 1993/6/1/entrez SP - 1333 EP - 9 JF - European journal of immunology JO - Eur J Immunol VL - 23 IS - 6 N2 - Following intraduodenal priming of mice with reovirus, precursor cytotoxic T lymphocytes (pCTL) rapidly appear in intraepithelial lymphocytes (IEL) and Peyer's patches. (unboundmedicine.com)
  • Adoptive transfer of Peyer's patch lymphocytes from normal BALB/c mice into reovirus-infected CB.17 severe combined immunodeficiency mice results in the infection-dependent appearance of large numbers of both CD8+Thy-1+ and CD8-Thy-1+, IEL that express the alpha/beta T cell receptor (TcR). (unboundmedicine.com)
  • Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes. (nih.gov)
  • These studies demonstrate that EtOH and nicotine have significant immunomodulatory effects on the cytotoxic activities of human lymphocytes which may be of clinical relevance. (nih.gov)
  • The first human tumor-associated antigen (TAA) to be discovered, recognized by cytotoxic CD8+ T lymphocytes (CTL), was MAGE-A1 which was identified from tumor-infiltrating lymphocytes obtained after culture of a melanoma biopsy [ 2 ]. (hindawi.com)
  • The proliferative response of human PBLs is also accompanied by the generation of potent cytotoxic activity against NK-sensitive and -resistant targets. (springer.com)
  • Bank G, Forsgren A. Many bacteria species are mitogenic for human blood B lymphocytes. (springer.com)
  • Räsänen L, Karhumäki E, Majuri R, Arvilommi H. Polyclonal activation of human lymphocytes by bacteria. (springer.com)
  • This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. (dovepress.com)
  • Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. (dovepress.com)
  • Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization. (dovepress.com)
  • Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. (jimmunol.org)
  • For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. (rcsb.org)
  • Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. (nii.ac.jp)
  • Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. (asm.org)
  • Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. (asm.org)
  • Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. (dovepress.com)
  • Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. (rupress.org)
  • Examination of mice with early-stage tumors or age-matched wild-type mice identified the increased presence of lymphocytes expressing the cytolytic molecule granzyme B (Gzmb) in transformed tissues. (aacrjournals.org)
  • This serine protease may have a role in lymphocyte lysis and a "lytic cascade. (sciencemag.org)
  • LEV had no influence on apoptosis and proliferation of CD8+ T lymphocytes (p﹥0.05). (uni-marburg.de)
  • Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. (frontiersin.org)
  • Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. (nih.gov)
  • Using limiting dilution analyses, it was estimated that 7 days after intraduodenal infection the average frequency of virus-specific pCTL was 197/10(6) CD8+Thy-1+ IEL and 190/10(6) CD8+Thy-1+ Peyer's patch lymphocytes. (unboundmedicine.com)
  • WELTE, A. y PRETORIUS, C. . A model of HIV infection with two viral strains and cytotoxic T-lymphocyte response under structured treatment interruptions . (scielo.org.za)
  • Cytotoxic innate lymphoid natural killers (NK) and adaptive CD8 + T lymphocytes (CTL) interact to elicit specific cytolytic outcomes. (frontiersin.org)
  • n=15) of CD8+ T lymphocytes after 2h of virus-peptide induced stimulation. (uni-marburg.de)
  • In cord blood T lymphocytes, induction of Jakmip1 occurs upon TCR/CD28 stimulation and parallels induction of effector proteins, such as granzyme B and perforin. (pasteur.fr)
  • Cytotoxic lymphocytes combat intracellular infections. (frontiersin.org)
  • Cytotoxic T lymphocytes (CTL) are essential for immune clearance of many intracellular pathogens, including most viruses and some bacteria ( 1 , 18 ). (asm.org)
  • Publications] Chipeta J, Komada Y, Zhang X, Azuma E, Sakurai M :'Intracellular cytokine profiles of cord and adult blood lymphocytes. (nii.ac.jp)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. (jci.org)
  • Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). (washington.edu)
  • Following intraduodenal priming of mice with reovirus, precursor cytotoxic T lymphocytes (pCTL) rapidly appear in intraepithelial lymphocytes (IEL) and Peyer's patches. (unboundmedicine.com)
  • Adams DH, Yannelli JR, Newman W, Lawley T, Ades E, Rosenberg SA and Shaw S (1997) Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis. (springer.com)
  • Degranulation of CD8+ T lymphocyte was indicated by perforin release and the increase of CD107a/b expression on the cell surface. (uni-marburg.de)
  • Conclusions: LEV showed a moderate attenuating effect on degranulation of CD8+ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. (uni-marburg.de)
  • To effect defense against pathogens both exogenous and endogenous, the adaptive immune system leverages the tremendous proliferative capacity with which it is endowed to generate terminally differentiated lymphocytes that potently eliminate or suppress threats to organismal health. (upenn.edu)