Defective survival of naive CD8 + T lymphocytes in the absence of the β3 regulatory subunit of voltage-gated calcium channels

T cell activation triggers large calcium fluxes. Flavell and colleagues show tonic calcium signaling via Ca v 1.4-β3 channels are needed for the survival and homeostasis of naive CD8 + T cells. The survival of T lymphocytes requires sustained, Ca 2+ influx–dependent gene expression. The molecular mechanism that governs sustained Ca 2+ influx in naive T lymphocytes is unknown. Here we report an essential role for the β3 regulatory subunit of voltage-gated calcium (Ca v ) channels in the maintenance of naive CD8 + T cells. Deficiency in β3 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 Ca 2+ entry in CD8 + T cells. Ca v 1.4 and β3 associated with T cell signaling machinery and Ca v 1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca 2+ entry is controlled by a Ca v 1.4-β3 channel complex in T cells.