Th17 cells undergo Fas-mediated activation-induced cell death independent of IFN-gamma.
IL-17-secreting CD4+ T cells (Th17 cells) play a critical role in immune responses to certain infections and in the development of many autoimmune disorders. The mechanisms controlling homeostasis in this cell population are largely unknown. In this study, we show that murine Th17 cells undergo rapid apoptosis in vitro upon restimulation through the TCR. This activation-induced cell death (AICD), a common mechanism for elimination of activated T cells, required the Fas and FasL interaction: Fas was stably expressed, while FasL was up-regulated upon TCR reactivation of Th17 cells; Ab ligation of Fas induced Th17 cell death; and AICD was completely absent in Th17 cells differentiated from gld/gld CD4+ T cells. Thus, the Fas/FasL pathway is essential in regulating the AICD of Th17 cells. Interestingly, IFN-gamma, a cytokine previously found to be important for the AICD of T cells, did not affect Th17 cell apoptosis. Furthermore, Th17 cells derived from mice deficient in IFN-gamma receptor 1 (IFN-gammaR1-/-) underwent AICD similar to wild-type cells. Thus, AICD of Th17 cells occurs via the Fas pathway, but is independent of IFN-gamma.
Zhang
Yingyu
Y
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Xu
Guangwu
G
Zhang
Liying
L
Roberts
Arthur I
AI
Shi
Yufang
Y
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020239:Receptor Cross-Talk / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D053222:Fas Ligand Protein; D007371:Interferon-gamma; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D019014:fas Receptor; D000096743:Interferon gamma Receptor