title: The tuberous sclerosis complex-mammalian target of rapamycin pathway maintains the quiescence and survival of naive T cells.
abstract: Naive T cells receive stimulation from the positive selecting ligand in the periphery for their survival. This stimulation does not normally lead to overt activation of T cells, as the T cells remain largely quiescent until they receive either antigenic or lymphopenic stimuli. The underlying mechanism responsible for survival and quiescence of the naive T cells remains largely unknown. In this study, we report that T cell-specific deletion of Tsc1, a negative regulator of mammalian target of rapamycin, resulted in both spontaneous losses of quiescence and cellularity, especially within the CD8 subset. The Tsc1-deficient T cells have increased cell proliferation and apoptosis. Tsc1 deletion affects the survival and quiescence of T cells in the absence of antigenic stimulation. Loss of quiescence but not cellularity was inhibited by rapamycin. Our data demonstrate that tuberous sclerosis complex-mammalian target of rapamycin maintains quiescence and survival of T cells.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Ikenoue
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.forename: Chi-Shan
authors.initials: CS
authors.lastname: Li
authors.forename: Weiquan
authors.initials: W
authors.lastname: Li
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018390:Gene Targeting; D007156:Immunologic Memory / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*
chemical_list: C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases