Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels.

The survival of T lymphocytes requires sustained, Ca2+ influx-dependent gene expression. The molecular mechanism that governs sustained Ca2+ influx in naive T lymphocytes is unknown. Here we report an essential role for the beta 3 regulatory subunit of voltage-gated calcium (Ca-v) channels in the maintenance of naive CD8(+) T cells. Deficiency in beta 3 resulted in a profound survival defect of CD8(+) T cells. This defect correlated with depletion of the pore-forming subunit Ca(v)1.4 and attenuation of T cell antigen receptor (TCR)-mediated global Ca2+ entry in CD8(+) T cells. Ca(v)1.4 and beta 3 associated with T cell signaling machinery and Ca(v)1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca2+ entry is controlled by a Ca(v)1.4-beta 3 channel complex in T cells.