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Fas expression on antigen-specific T cells has costimulatory, helper, and down-regulatory functions in vivo for cytotoxic T cell responses but not for T cell-dependent B cell responses Puliaeva I; Puliaev R; Shustov A; Haas M; Via CSJ Immunol 2008[Nov]; 181 (9): 5912-29Fas-mediated apoptosis is an important contributor to contraction of Ag-driven T cell responses acting only on activated Ag-specific T cells. The effects of targeted Fas deletion on selected cell populations are well described however little is known regarding the consequences of Fas deletion on only activated Ag-specific T cells. We addressed this question using the parent-into-F(1) (P-->F(1)) model of acute or chronic (lupus-like) graft-vs-host disease (GVHD) as a model of either a CTL-mediated or T-dependent B cell-mediated response, respectively. By transferring Fas-deficient lpr donor T cells into Fas-intact F(1) hosts, the in vivo role of Ag-specific T cell Fas can be determined. Our results demonstrate a novel dichotomy of Ag-specific T cell Fas function in that: 1) Fas expression on Ag-activated T cells has costimulatory, helper, and down-regulatory roles in vivo and 2) these roles were observed only in a CTL response (acute GVHD) and not in a T-dependent B cell response (chronic GVHD). Specifically, CD4 T cell Fas expression is important for optimal CD4 initial expansion and absolutely required for help for CD8 effector CTL. Donor CD8 T cell Fas expression played an important but not exclusive role in apoptosis and down-regulation. By contrast, CD4 Fas expression played no detectable role in modulating chronic GVHD induction or disease expression. These results demonstrate a novel role for Ag-specific T cell Fas expression in in vivo CTL responses and support a review of the paradigm by which Fas deficiency accelerates lupus in MRL/lpr lupus-prone mice.|Acute Disease[MESH]|Animals[MESH]|B-Lymphocytes/*immunology/metabolism[MESH]|CD4-Positive T-Lymphocytes/*immunology/metabolism/transplantation[MESH]|Cell Line, Tumor[MESH]|Cells, Cultured[MESH]|Crosses, Genetic[MESH]|Down-Regulation/genetics/*immunology[MESH]|Epitopes, T-Lymphocyte/administration & dosage/*immunology[MESH]|Graft vs Host Disease/genetics/immunology/mortality[MESH]|Lupus Nephritis/genetics/immunology/pathology[MESH]|Lymphocyte Activation/genetics/*immunology[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mice, Inbred MRL lpr[MESH]|T-Lymphocytes, Cytotoxic/*immunology/metabolism/transplantation[MESH]|T-Lymphocytes, Helper-Inducer/*immunology/metabolism[MESH]|fas Receptor/*biosynthesis/genetics/physiology[MESH] |
