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

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 p21(Cip1). Our data define a CSN-dependent pathway of transcriptional control that is essential for antigen-induced initiation of T cell proliferation.