The tuberous sclerosis complex-mammalian target of rapamycin pathway maintains the quiescence and survival of naive T cells

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 mechani...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2011-08, Vol.187 (3), p.1106-1112
Main Authors: Wu, Qi, Liu, Yu, Chen, Chong, Ikenoue, Tsuneo, Qiao, Yu, Li, Chi-Shan, Li, Weiquan, Guan, Kun-Liang, Liu, Yang, Zheng, Pan
Format: Article
Language:English
Subjects:
Animals
CD4-CD8 Ratio
Cell Survival - genetics
Cell Survival - immunology
Cells, Cultured
Gene Targeting
Immunologic Memory - genetics
Lymphopenia - genetics
Lymphopenia - immunology
Lymphopenia - pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Resting Phase, Cell Cycle - genetics
Resting Phase, Cell Cycle - immunology
Signal Transduction - genetics
Signal Transduction - immunology
T-Lymphocyte Subsets - enzymology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - pathology
TOR Serine-Threonine Kinases - physiology
Tumor Suppressor Proteins - antagonists & inhibitors
Tumor Suppressor Proteins - deficiency
Tumor Suppressor Proteins - physiology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1003968