Low-Voltage-Activated Ca_V3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles

Activation of T cells is mediated by the engagement of T cell receptors (TCRs) followed by calcium entry via store-operated calcium channels. Here we have shown an additional route for calcium entry into T cells-through the low-voltage-activated T-type Ca_V3.1 calcium channel. Ca_V3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for Ca_V3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells. Ca_V3.1 deficiency led to decreased secretion of GM-CSF from in vitro polarized Th1 and Th17 cells. Nuclear translocation of the nuclear factor of activated T cell (NFAT) was also reduced in Ca_V3.1-deficient T cells. These data provide evidence for T-type channels in immune cells and their potential role in shaping the autoimmune response.