细胞生物学
信号转导衔接蛋白
T细胞
平衡
CD8型
细胞毒性T细胞
生物
化学
信号转导
免疫系统
免疫学
体外
生物化学
作者
Thomas M. Yankee,Theodore J. Yun,Kevin E. Draves,Kolumam Ganesh,Michael J. Bevan,Kaja Murali‐Krishna,Edward A. Clark
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2004-08-01
卷期号:173 (3): 1711-1720
被引量:24
标识
DOI:10.4049/jimmunol.173.3.1711
摘要
Abstract Little is known about the role of the Gads (GrpL) adaptor protein in mature T cell populations. In this study we show that the effects of Gads deficiency on murine CD4+ and CD8+ T cells are markedly different. Gads−/− CD4+ T cells were markedly deficient in the spleen and had an activated phenotype and a rapid turnover rate. When transferred into a wild-type host, Gads−/− CD4+ T cells continued to proliferate at a higher rate than wild-type CD4+ T cells, demonstrating a defect in homeostatic proliferation. Gads−/− CD8+ T cells had a memory-like phenotype, produced IFN-γ in response to ex vivo stimulation, and underwent normal homeostatic proliferation in wild-type hosts. Gads−/− T cells had defective TCR-mediated calcium responses, but had normal activation of ERK. Gads−/− CD4+ T cells, but not CD8+ T cells, had a severe block of TCR-mediated proliferation and a high rate of spontaneous cell death and were highly susceptible to CD95-induced apoptosis. This suggests that the rapid turnover of Gads−/− CD4+ T cells is due to a defect in cell survival. The intracellular signaling pathways that regulate homeostasis in CD4+ and CD8+ T cells are clearly different, and the Gads adaptor protein is critical for homeostasis of CD4+ T cells.
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