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Nature Immunology 8, 1236–1245 (1 November 2007) | doi:10.1038/ni1514

COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor|[ndash]|induced entry into the cell cycle from quiescence

Suchithra Menon , Hongbo Chi , Huiyong Zhang , Xing Wang Deng , Richard A Flavell & Ning Wei

Engagement of antigen receptors triggers the proliferation and functional activation of lymphocytes. Here we report that T cell homeostasis and antigen-induced responses require the COP9 signalosome (CSN), a regulator of the ubiquitin-proteasome system. Conditional deletion of the CSN subunit Csn8 in peripheral T lymphocytes disrupted formation of the CSN complex, reduced T cell survival and proliferation in vivo and impaired antigen-induced production of interleukin 2. Moreover, Csn8-deficient T cells showed defective entry into the cell cycle from the G0 quiescent state. This phenotype was associated with a lack of signal-induced expression of cell cycle–related genes, including G1 cyclins and cyclin-dependent kinases, and with excessive induction of p21Cip1. Our data define a CSN-dependent pathway of transcriptional control that is essential for antigen-induced initiation of T cell proliferation.