title: The Gads (GrpL) adaptor protein regulates T cell homeostasis.
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-gamma 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.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Yankee
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Yun
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Draves
authors.forename: Kolumam
authors.initials: K
authors.lastname: Ganesh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
authors.forename: Kaja
authors.initials: K
authors.lastname: Murali-Krishna
authors.forename: Edward A
authors.initials: EA
authors.lastname: Clark
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006706:Homeostasis; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; C498726:Mona protein, mouse; D019014:fas Receptor