Topic
Cytotoxic T cell
About: Cytotoxic T cell is a research topic. Over the lifetime, 92492 publications have been published within this topic receiving 4768477 citations. The topic is also known as: killer T cell & cytotoxic T lymphocyte.
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TL;DR: Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator of the genetic program governing CD25+CD4+ regulatory T cell (T(R)) development and function in mice and the relationship between FOXP3 expression and human T(R) development is addressed.
Abstract: Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator of the genetic program governing CD25+CD4+ regulatory T cell (Tr) development and function in mice. In humans, its role in mediating Tr development has been controversial. Furthermore, the fate of Tr precursors in FOXP3 deficiency has yet to be described. Making use of flow cytometric detection of human FOXP3, we have addressed the relationship between FOXP3 expression and human Tr development. Unlike murine Foxp3− T cells, a small subset of human CD4+ and CD8+ T cells transiently up-regulated FOXP3 upon in vitro stimulation. Induced FOXP3, however, did not alter cell-surface phenotype or suppress T helper 1 cytokine expression. Furthermore, only ex vivo FOXP3+ Tr cells persisted after prolonged culture, suggesting that induced FOXP3 did not activate a Tr developmental program in a significant number of cells. FOXP3 flow cytometry was also used to further characterize several patients exhibiting symptoms of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) with or without FOXP3 mutations. Most patients lacked FOXP3-expressing cells, further solidifying the association between FOXP3 deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Interestingly, one patient bearing a FOXP3 mutation enabling expression of stable FOXP3mut protein exhibited FOXP3mut-expressing cells among a subset of highly activated CD4+ T cells. This observation raises the possibility that the severe autoimmunity in FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that have developed from Tr precursors.
777 citations
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TL;DR: This work has defined the cytokine transforming growth factor-beta as a critical regulator of thymic T cell development as a crucial player in peripheral T cell homeostasis, tolerance to self antigens, and T cell differentiation during the immune response.
774 citations
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TL;DR: The dramatic reversal of EBV-driven lymphoproliferations in bone marrow transplant patients following CTL infusion demonstrates the potential of this approach, and prospects for its extension to otherEBV-positive tumors in which the immunodominant EBNA3A, 3B, 3C proteins are not expressed are discussed.
Abstract: ▪ Abstract Epstein-Barr virus (EBV) provides one of the most informative systems with which to study cytotoxic T lymphocyte (CTL) responses in humans. The virus establishes a highly immunogenic growth-transforming infection of B lymphocytes, associated with the coordinate expression of six virus-coded nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, -LP) and two latent membrane proteins (LMPs 1 and 2). This elicits both primary and memory CT8+ CTL responses that are markedly skewed toward HLA allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins, with reactivities to other antigens being generally much less frequent. This heirarchy of immunodominance among the different latent proteins may at least partly reflect their differential accessibility to the HLA class I–processing pathway. Furthermore, CTLs to some of the immunodominant epitopes involve highly conserved T cell receptor (TCR) usage, a level of focusing which evidence suggests could have immunopathological consequences from cr...
773 citations
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TL;DR: The results broaden the immunoregulatory role played by CD4+CD25+ T cells in the prevention of autoimmune diseases, but also raise the possibility that they may hinder the induction of effector CD8- T cells to tumor or foreign Ags.
Abstract: CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) T cells and are potent suppressors of CD4(+)CD25(-) T cell activation in vitro. We demonstrate that CD4(+)CD25(+) T cells also suppress both proliferation and IFN-gamma production by CD8(+) T cells induced either by polyclonal or Ag-specific stimuli. CD4(+)CD25(+) T cells inhibit the activation of CD8(+) responders by inhibiting both IL-2 production and up-regulation of IL-2Ralpha-chain (CD25) expression. Suppression is mediated via a T-T interaction as activated CD4(+)CD25(+) T cells suppress the responses of TCR-transgenic CD8(+) T cells stimulated with soluble peptide-MHC class I tetramers in the complete absence of APC. These results broaden the immunoregulatory role played by CD4(+)CD25(+) T cells in the prevention of autoimmune diseases, but also raise the possibility that they may hinder the induction of effector CD8(+) T cells to tumor or foreign Ags.
771 citations
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TL;DR: It is demonstrated for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo, thereby promoting metastasis and surface shielding by platelet aggregates seems to be the main mechanism.
Abstract: Natural killer (NK) cells provide effective antitumoral activity in the blood stream of mice, leading to reduced metastasis. There are, however, tumor cells that metastasize despite the presence of an intact NK system. The capability of tumor cells to induce platelet aggregation, on the other hand, correlates with their enhanced metastatic potential. A counteractive role of platelets for the NK function in metastasis has never been conceived. Here we demonstrate for the first time that platelets directly protect tumor cells from NK lysis in vitro as well as in vivo. Using three different tumor cell lines in a mouse model of experimental metastasis, tumor seeding in the target organs was reduced when the host was platelet depleted, but only if the tumor cells were NK sensitive. Aggregation of platelets around tumor cells also inhibited in vitro NK tumorilytic activity. This protection of tumor cells by platelets was mouse strain independent and was equally observed with platelets from β2-microglobulin-deficient mice, excluding a NK inhibitory function of MHC class I on platelets. Thus, even if tumor cells are NK susceptible and cytotoxic NK cells threaten their survival in the blood, platelets are capable of protecting them from cytolysis, thereby promoting metastasis. Surface shielding by platelet aggregates seems to be the main mechanism of this protection.
769 citations