Requirement of voltage-gated calcium (Cav) channels in T cell receptor-mediated calcium response and effector functions of T lymphocytes

Calcium signals are required for the activation, differentiation and effector functions of T lymphocytes. However, the molecular machinery required for calcium influx upon TCR stimulation of T cells is not yet clear. Previously, we have shown that members of the Cav1 family of voltage-gated calcium channels are expressed in T lymphocytes and regulate calcium influx into these cells. Recently, we have demonstrated an essential role for the beta3 regulatory subunit of Cav channels in the maintenance of naive CD8 T cells since deficiency in beta3 resulted in a profound survival defect of naive CD8 T cells. Here, we investigated the expression and function of Cav1 channels in differentiated CD4 T lymphocyte populations and discovered a novel role of Cav1 channels in effector helper T cell population. We found a selective expression of Cav1.3 in effector Th2 cells but not naive CD4 T cells or effector Th1 cells. Both TCR-mediated calcium response and NFATs nuclear localization were severely impaired in Cav1.3-deficient Th2 cells. A profound and selective impairment of Th2 effector cytokine production was observed in vitro and in vivo after immunization of mice. Our data demonstrate a novel and essential role of Cav1 channels in different T cell functions. Therefore, Cav1 channels represent a specific and new therapeutic target for T cell-mediated inflammatory diseases.