The vitamin D receptor turns off chronically activated T cells

T cell proliferation and T helper (T-H) cells that make IL-17 (T(H)17 cells) and IFN-gamma (T(H)1 cells) have been shown to be inhibited by 1,25(OH)(2)D-3. Previous work has shown that immune-mediated diseases, where T(H)1 and T(H)17 cells are pathogenic, are ameliorated with 1,25(OH)(2)D-3 treatment. Paradoxically, infectious diseases that require T(H)1 and T(H)17 responses for host resistance are unaffected by 1,25(OH)(2)D-3 treatment. Resting T cells are not responsive to vitamin D because they do not express the vitamin D receptor (VDR) until late after activation. T cells activated following an infection help clear the infection, and since the antigen is eliminated, vitamin D is not needed to dampen the immune response. Conversely, in immune-mediated disease, there is chronic T cell activation, and in this scenario, vitamin D and 1,25(OH)(2)D-3 are critical for inhibiting T cell proliferation and cytokine production. Vitamin D is a late regulator of T cell function and acts to turn off T cells. This paper will review these data.