학술논문
The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function.
Document Type
Article
Source
Subject
*HOMEOSTASIS
*T cells
*TUMOR suppressor genes
*ANTIGENS
*APOPTOSIS
*IMMUNE response
*BACTERIAL diseases
*CELL cycle
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Language
ISSN
1529-2908
Abstract
The mechanisms that regulate T cell quiescence are poorly understood. We report that the tumor suppressor Tsc1 established a quiescence program in naive T cells by controlling cell size, cell cycle entry and responses to stimulation of the T cell antigen receptor. Abrogation of quiescence predisposed Tsc1-deficient T cells to apoptosis that resulted in loss of conventional T cells and invariant natural killer T cells. Loss of Tsc1 function dampened in vivo immune responses to bacterial infection. Tsc1-deficient T cells had more activity of the serine-threonine kinase complex mTORC1 but less mTORC2 activity, and activation of mTORC1 was essential for the disruption of immune homeostasis. Therefore, Tsc1-dependent control of mTOR is crucial in actively maintaining the quiescence of naive T cells to facilitate adaptive immune function. [ABSTRACT FROM AUTHOR]