• cells
  • However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. (rupress.org)
  • Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8 + T cells can be regulated by innate immunity and the gut microbiota. (rupress.org)
  • However, there is a substantial gap in our knowledge of how islet autoimmunity mediated by CD8 + T cells is shaped by innate immunity and the gut microbiota. (rupress.org)
  • Suppression of immune responses by CD8 cells. (nii.ac.jp)
  • Of particular interest is human histocompatibility leukocyte antigen (HLA)-G which is expressed on placental cytotrophoblast cells. (rupress.org)
  • In this report, we demonstrate that CD8 can bind to HLA-G. It is possible, therefore, that a cell bearing CD8 may interact with HLA-G-expressing cells. (rupress.org)
  • Furthermore, development of a protocol for rapid identification of high avidity human and murine T cells using tetramers with impaired CD8 binding provides an opportunity not only to monitor expansion of high avidity T cell responses ex vivo, but also to sort high avidity CTL clones for adoptive T cell transfer therapy. (ox.ac.uk)
  • By transgenic expression of ovalbumin (OVA) as a model self antigen in the β cells of the pancreas, we have shown that self tolerance can be maintained by the cross-presentation of this antigen on dendritic cells in the draining lymph nodes. (rupress.org)
  • Deletion of CD8 T cells was prevented by overexpression of Bcl-2, indicating that cross-tolerance was mediated by a Bcl-2 inhibitable pathway. (rupress.org)
  • Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance. (rupress.org)
  • CD8 T cells recognize antigen presented by MHC class I molecules. (rupress.org)
  • In an immunogenic response, the advantage of cross-presentation is that proteins from pathogens that do not infect DCs can still be processed in the MHC class I pathway of such professional APCs, allowing them to prime naive CD8 T cells, a process termed cross-priming ( 4 ). (rupress.org)
  • This creates the potential for autoimmunity when antigens whose expression is limited to peripheral tissues are cross-presented to autoreactive CD8 T cells. (rupress.org)
  • However, we have shown that cross-presentation of self antigen leads to deletion of naive, autoreactive CD8 T cells. (rupress.org)
  • This process, termed cross-tolerance, is preceded by the activation and limited proliferation of autoreactive CD8 T cells ( 5 , 6 ). (rupress.org)
  • Our study seeks to further understand the molecular mechanisms underlying the deletion of CD8 T cells by cross-tolerance. (rupress.org)
  • Apoptosis is involved in many aspects of the control of peripheral T cell numbers including: normal cell turnover in naive (unimmunized) animals, reduction of the pool of activated, antigen-specific T cells at the termination of an immune response, and maintenance of peripheral tolerance to tissue antigens ( 7 , 8 ). (rupress.org)
  • The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation even though virus-derived antigens (Ags) are still presented by DCs long after acute infection is resolved. (rupress.org)
  • However, the effects of extended Ag presentation on CD8 T cells are undefined and the mechanisms that regulate prolonged Ag presentation are unknown. (rupress.org)
  • Although prolonged Ag presentation did not alter the number of memory CD8 T cells that developed, it was essential for programming the capacity of these cells to proliferate, produce cytokines, and protect the host after secondary challenge. (rupress.org)
  • Collectively, our results demonstrate that B cells and Abs can regulate the quality and functionality of a subset of antiviral CD8 T cell memory responses and do so by promoting sustained Ag presentation by DCs during the contraction phase of the primary T cell response. (rupress.org)
  • Antigen (Ag) processing and presentation is essential for the activation and differentiation of T cells. (rupress.org)
  • Although many cell types can function as APCs for CD8 T cells, naive T cells are initially activated by DCs ( Lanzavecchia and Sallusto, 2001 ). (rupress.org)
  • However, CD8 T cells responding to natural infections, such as influenza, rarely encounter Ag for such a brief period. (rupress.org)
  • This process leads to the contraction of the acute effector CD8 T cell response and the survival of a much smaller cohort of memory CD8 T cells ( Harty and Badovinac, 2008 ). (rupress.org)
  • These memory CD8 T cells are poised to rapidly respond to secondary encounter with Ag, in part because they receive programming signals during the primary response which imprints the cells with the ability to rapidly proliferate and exert effector functions ( Arens and Schoenberger, 2010 ). (rupress.org)
  • Although our knowledge of the diversity in cytokine production by CD8 T cells lags behind CD4 T cells, they too have been reported to fall into two subpopulations based on cytokine secretion so that T cytotoxic type 1 (Tc1) CD8 T cells secrete IFN- g , whereas Tc2 secrete IL-4 (1-5). (kserre.net)
  • Some studies have reported a poor ability of alum-protein vaccines to induce cytotoxic CD8 T cell-responses (6, 7), while we and others have shown that antigen-specific adoptively transferred transgenic CD8 T cells (8) and endogenous CD8 T cells proliferate (9) as well as develop cytotoxicity (10) in response to this form of antigen. (kserre.net)
  • Our approach has been to compare the polarization of transgenic naïve ovalbumin-specific CD4 (OTII) and CD8 (OTI) T cells. (kserre.net)
  • CD4 T cells were induced to produce Th2 cytokines by this antigen. (kserre.net)
  • This is consistent with other studies assessing the proportion of IL-4-containing OTII cells in response to the same antigen (8, 11, 12). (kserre.net)
  • These results show that OTI cells responding to alumOVA in vivo fail to mimic the Th2 response of OTII cells responding to this same antigen, but acquire Th1-related features. (kserre.net)
  • This contrasts with failure of the OTI cells responding to alumOVA in vivo , to mimic the Th2 response of OTII cells responding to this antigen. (kserre.net)
  • Chimeric antigen receptor-modified T cells derived from defined CD8(+) and CD4(+) subsets confer superior antitumor reactivity in vivo. (fredhutch.org)
  • Adoptive T-cell therapy with gene-modified T-cells expressing a tumor-reactive T-cell receptor (TCR) or chimeric antigen receptor (CAR) is a rapidly growing field of translational medicine and has shown success in the treatment of B-cell malignancies and solid tumors. (fredhutch.org)
  • In all reported trials, patients have received T-cell products comprised of random compositions of CD4(+) and CD8(+) naïve and memory T-cells, meaning that each patient received a different therapeutic agent. (fredhutch.org)
  • We analyzed CD19 CAR-expressing effector T-cells derived from different subsets (CD4(+)/CD8(+) naïve, central memory, effector memory). (fredhutch.org)
  • Although the contribution of CD8(+) T cells to the pathogenesis of noncommunicable lung diseases has become increasingly appreciated, our knowledge about the mechanisms controlling self-reactive CD8(+) T cells in the respiratory tract remains largely elusive. (fu-berlin.de)
  • We found that CD8(+) T cells remain ignorant in the steady state, whereas transient proliferation of self-reactive CD8(+) T cells is induced by forced maturation or licensing of dendritic cells, increases in the antigenic threshold, and targeted release of alveolar self-antigen by epithelial injury. (fu-berlin.de)
  • We conclude that inadvertent activation of CD8(+) T cells in the lung is prevented in the absence of 'danger signals,' whereas tissue damage after infection or noninfectious inflammation creates an environment that allows the priming of previously ignorant T cells. (fu-berlin.de)
  • Although multiple trials of cancer vaccines, particularly using short peptides recognized by CD8 + T cells, have resulted in the development of measurable immune responses, only a minority of patients has experienced clinical benefit such as tumor regression. (aacrjournals.org)
  • In some experiments, vaccination with peptides recognized by CD8 + T cells caused enhanced tumor outgrowth associated with peptide-induced tolerance. (aacrjournals.org)
  • Whereas peptide immunization with an H2-D d -restricted CTL epitope derived from NY-ESO-1 (NY-ESO-1 p81-88) induced NY-ESO-1 81-88 -specific CD8 + T cells in draining lymph nodes and spleens, tumor growth was significantly enhanced. (aacrjournals.org)
  • 80% of NY-ESO-1 81-88 -specific CD8 + T cells at tumor sites and repetitive immunization further diminished the number of specific CD8 + T cells. (aacrjournals.org)
  • These augmented anti-tumor responses were correlated with CpG-induced DC maturation, as CpG-matured DCs, but not immature DCs could reduced Fas and PD-1 expression on the surface of antigen-specific CD8 + T cells. (aacrjournals.org)
  • On the other hand, CD4 − CD8 T cells may be required for the proliferation of PBLs and generation of cytotoxic effector cells. (springer.com)
  • They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells, which then destroy the infectious particle. (wikipedia.org)
  • T cells displaying CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I (they are MHC class II-restricted). (wikipedia.org)
  • CD4 is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. (wikipedia.org)
  • It associates with the cytoplasmic tails of the CD4 and CD8 co-receptors on T helper cells and cytotoxic T cells, respectively, to assist signaling from the T cell receptor (TCR) complex. (wikipedia.org)
  • Rudd was the first to discover that intracellular protein kinases interact with surface receptors, by identifying the interaction of T-cell co-receptors CD4 (also the receptor for the human immunodeficiency virus, HIV-1) and CD8 on T-cells with protein-tyrosine kinase p56lck. (wikipedia.org)
  • In terms of immunology, the CD4- and CD8-p56lck complexes are now widely accepted as the initiators of the T cell activation, leading to the recruitment of a second tyrosine kinase ZAP-70 that control the ability of T-cells to respond to foreign pathogens, foreign transplants and cancer cells. (wikipedia.org)
  • Cross-presentation is the ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). (wikipedia.org)
  • Cross-presentation is of particular importance, because it permits the presentation of exogenous antigens, which are normally presented by MHC II on the surface of infected dendritic cells to be also presented by MHC I without infecting the dendritic cell. (wikipedia.org)
  • This resulted in CD8 T cell responses that were induced by antigen-presenting cells of the recipient, implying that these must have taken up and processed the injected cells. (wikipedia.org)
  • Even though many viruses can inhibit and degrade dendritic cell activity, cross-presenting dendritic cells that are unaffected by the virus are able to intake the infected dendritic cell and still cross present the antigen to T cells. (wikipedia.org)
  • The action of cross priming can bolster immunity against antigens that target dendritic cells in order to inhibit maturation and an immune response from T cells. (wikipedia.org)
  • Some self-antigens (autoantigens) are cross-presented, resulting in the elimination of autoreactive CD8 T cells. (wikipedia.org)
  • Finally, MHC class I-peptide complexes are transported to the cell surface, where they can be detected by specific CD8 T cells. (wikipedia.org)
  • There is evidence that suggest that cross-presentation requires cytosolic diversion in a proportion of CD8(+) dendritic cells that are able to cross-present. (wikipedia.org)
  • In the capable dendritic cells, cytosolic diversion is the name of the process that diverts antigens away from the route in which they are guided for antigen presentation by MHC II by being transported for release into the cytoplasm following endocytosis for degradation by the proteasomes necessary for MHC I antigen presentation (cross-presentation). (wikipedia.org)
  • In addition, IL-21 producing virus specific CD8 T cells were also preferentially found in HIV controllers. (wikipedia.org)
  • TNF-α is produced by infected macrophages and the interaction between dendritic cells presenting the antigen to CD8 (T Killer cells). (wikipedia.org)
  • Identified the first cell surface antigens distinguishing cells of different lineages, introducing the concept of cell surface antigens that could differentiate different cell types. (wikipedia.org)
  • CD8 cells, often referred to as "killer" T cells, are one of the major cells of the adaptive immune response, and are capable of directly killing dangerous or foreign cells (1964-1968). (wikipedia.org)
  • CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. (wikipedia.org)
  • They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells. (wikipedia.org)
  • CD1a, CD1b and CD1c (group 1 CD1 molecules) are expressed on cells specialized for antigen presentation. (wikipedia.org)
  • Group 1 CD1 molecules have been shown to present foreign lipid antigens, and specifically a number of mycobacterial cell wall components, to CD1-specific T cells. (wikipedia.org)
  • Natural Killer T (NKT) cells are activated by CD1d-presented antigens, and rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and IL-4 production. (wikipedia.org)
  • CD1 antigens are expressed on cortical thymocytes, but not on mature T cells. (wikipedia.org)
  • This often remains true in neoplastic cells from these populations, so that the presence of CD1 antigens can be used in diagnostic immunohistochemistry to identify some thymomas and malignancies arising from T cell precursors. (wikipedia.org)
  • These cells have antibodies present on the surface of the extracellular membrane, which contribute to the destruction of the invader or antigen. (wikipedia.org)
  • T-cell antibodies bind to antigens such as virus infected cells or tumor cells. (wikipedia.org)
  • In Lutzner cells, there is a mutation in the T-cell receptor that inhibits antigens like CD8 and CD7, but stimulates the over production of other antigens like CD4. (wikipedia.org)
  • Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. (wikipedia.org)
  • An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. (wikipedia.org)
  • Instead, the DNA in millions of white blood cells in the bone marrow is shuffled to create cells with unique receptors, each of which can bind to a different antigen. (wikipedia.org)
  • The vast majority of T cells express alpha-beta TCRs (αβ T cells), but some T cells in epithelial tissues (like the gut) express gamma-delta TCRs (γδ T cells), which recognize non-protein antigens. (wikipedia.org)
  • T cells with functionally stable TCRs express both the CD4 and CD8 co-receptors and are therefore termed "double-positive" (DP) T cells (CD4+CD8+). (wikipedia.org)
  • The double-positive T cells are exposed to a wide variety of self-antigens in the thymus and undergo two selection criteria: positive selection, in which those double-positive T cells that bind to foreign antigen in the presence of self MHC. (wikipedia.org)
  • In this case, the cells would have been presented antigen in the context of MHC1. (wikipedia.org)
  • negative selection, in which those double-positive T cells that bind too strongly to MHC-presented self antigens undergo apoptosis because they could otherwise become autoreactive, leading to autoimmunity. (wikipedia.org)
  • Only those T cells that bind to the MHC-self-antigen complexes weakly are positively selected. (wikipedia.org)
  • Those cells that survive positive and negative selection differentiate into single-positive T cells (either CD4+ or CD8+), depending on whether their TCR recognizes an MHC class I-presented antigen (CD8) or an MHC class II-presented antigen (CD4). (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)
  • When these cells are infected with a virus (or another intracellular pathogen), the cells degrade foreign proteins via antigen processing. (wikipedia.org)
  • These result in peptide fragments, some of which are presented by MHC Class I to the T cell antigen receptor (TCR) on CD8+ T cells. (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)
  • Normally the immune system reacts to foreign antigens that are associated with exogenous or endogenous Danger signals, which triggers a proliferation of antigen-specific CD8+ T cells and/or CD4+ helper cells. (wikipedia.org)
  • PD-L1 binding to PD-1 also contributes to ligand-induced TCR down-modulation during antigen presentation to naive T cells, by inducing the up-regulation of the E3 ubiquitin ligase CBL-b. (wikipedia.org)
  • The presence of the antigen on tumor cells has been associated with worse prognosis. (wikipedia.org)
  • receptor
  • In this study, using islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8 + T cell-mediated T1D development via the gut microbiota. (rupress.org)
  • The data support a stabilizing role of CD8 through its binding to the same class I (but not class II) molecule on the target cell bound by the T cell antigen receptor. (rupress.org)
  • Genes associated with various biological and molecular processes including oxidative phosphorylation, T- and B- cell receptor signaling and antigen presentation were observed to significantly change with thymocyte age. (medsci.org)
  • When the T cell receptor is engaged by the specific antigen presented by MHC, Lck acts to phosphorylate the intracellular chains of the CD3 and ζ-chains of the TCR complex, allowing another cytoplasmic tyrosine kinase called ZAP-70 to bind to them. (wikipedia.org)
  • influenza
  • Nventa is also developing two additional therapeutic vaccine programs based on its CoVal technology-a Hsp - HBV (hepatitis B) fusion, and prototypes of Hsp fusion proteins with influenza antigens. (wikipedia.org)
  • vivo
  • Combining the most potent CD4(+) and CD8(+) CAR-expressing subsets resulted in synergistic antitumor effects in vivo. (fredhutch.org)
  • Humans
  • Most notably, Dr. Old discovered the LY-B antigen, later renamed CD8 in humans. (wikipedia.org)
  • Because of this and the fact that cows are a natural host of Mycobacterium bovis, a pathogen in humans as well, it is hoped that studying cows will yield insights into the group 1 CD1 antigen-presenting system. (wikipedia.org)
  • molecule
  • Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts. (rupress.org)
  • The TCR complex and CD4 each bind to distinct regions of the antigen-presenting MHCII molecule - α1/β1 and β2, respectively. (wikipedia.org)
  • 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. (wikipedia.org)
  • 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. (wikipedia.org)
  • The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation. (wikipedia.org)
  • protein
  • The functions of CD8 in the TCR complex are thought to be signaling through the association of CD8 with the protein tyrosine kinase p56lck and adhesion to MHC class I through the alpha 3 domain. (rupress.org)
  • This question is of interest because CD8 T cell response to alum-precipitated protein is under debate. (kserre.net)
  • It is also required for induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination. (wikipedia.org)
  • peptide
  • In the present study, we analyzed NY-ESO-1 peptide vaccinations using a new tumor model of BALB/c transplanted tumors expressing NY-ESO-1, which is a cancer/testis (CT) antigen discovered by SEREX (serological identification of antigens by recombinant expression cloning) using the serum of an esophageal cancer patient. (aacrjournals.org)
  • mice
  • It has been shown that IL-21R knock-out mice express higher levels of IgE and lower levels of IgG1 than normal mice after antigen exposure. (wikipedia.org)
  • endogenous
  • Access of antigen to the MHC class I presentation pathway was originally thought to be restricted to endogenous proteins, i.e., those expressed within the cytoplasm of the cell presenting the antigen. (rupress.org)
  • selectively
  • In this report, tetramers with mutated CD8 binding site selectively stain higher avidity human and murine CTL capable of recognizing physiological levels of Ag. (ox.ac.uk)
  • Antibodies
  • Once this antigen is lost, the T-cell antibodies will never be able to detect the pathogen, allowing the pathogen to increase in size and cause an infection to occur. (wikipedia.org)
  • clones
  • The results indicate that these clones display dual recognition for HLA-B27.1 and for HLA-DR2 and suggest that HLA-B27.1 may share at least one epitope that is closely related to some stimulatory Dw determinants present on the HLA-DR2 antigens. (rupress.org)