Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Immunol. 2011 Aug 1;187(3):1106-12. doi: 10.4049/jimmunol.1003968. Epub 2011 Jun 27.
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.
幼稚 T 细胞在外周接受正向选择配体的刺激以维持其存活。这种刺激通常不会导致 T 细胞明显活化，因为 T 细胞在接受抗原或淋巴缺失刺激之前，大部分处于静止状态。幼稚 T 细胞存活和静止的潜在机制在很大程度上仍不清楚。在这项研究中，我们报告称，T 细胞特异性敲除雷帕霉素靶蛋白（mammalian target of rapamycin）的负调节剂 Tsc1，会导致幼稚 T 细胞自发失去静止状态和细胞数量，尤其是在 CD8 亚群中。Tsc1 缺陷型 T 细胞的增殖和凋亡增加。在没有抗原刺激的情况下，Tsc1 缺失会影响 T 细胞的存活和静止状态。雷帕霉素可抑制 T 细胞失去静止状态，但不影响细胞数量。我们的数据表明，结节性硬化复合物-雷帕霉素靶蛋白复合体维持 T 细胞的静止和存活。
