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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Nov 01; Vol. 181 (9), pp. 5912-29. - Publication Year :
- 2008
-
Abstract
- Fas-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.
- Subjects :
- Acute Disease
Animals
B-Lymphocytes metabolism
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes transplantation
Cell Line, Tumor
Cells, Cultured
Crosses, Genetic
Down-Regulation genetics
Epitopes, T-Lymphocyte administration & dosage
Graft vs Host Disease genetics
Graft vs Host Disease immunology
Graft vs Host Disease mortality
Lupus Nephritis genetics
Lupus Nephritis immunology
Lupus Nephritis pathology
Lymphocyte Activation genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
T-Lymphocytes, Cytotoxic metabolism
T-Lymphocytes, Cytotoxic transplantation
T-Lymphocytes, Helper-Inducer metabolism
fas Receptor genetics
fas Receptor physiology
B-Lymphocytes immunology
CD4-Positive T-Lymphocytes immunology
Down-Regulation immunology
Epitopes, T-Lymphocyte immunology
Lymphocyte Activation immunology
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Helper-Inducer immunology
fas Receptor biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 181
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18941180
- Full Text :
- https://doi.org/10.4049/jimmunol.181.9.5912