期刊
JOURNAL OF IMMUNOLOGY
卷 173, 期 3, 页码 1711-1720出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.3.1711
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCRR NIH HHS [P51 RR000166-360067, RR01666] Funding Source: Medline
- NIAID NIH HHS [R01 AI019335-19, AI44257, R01 AI045088-01A1, R01 AI044257-05, AI45088] Funding Source: Medline
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-gamma in response to ex vivo stimulation, and underwent normal homeostatic proliferation in wild-type hosts. Gads(-/-) 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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