1,25-Dihydroxyvitamin D3 (calcitriol) suppresses IL-2 induced murine thymocyte proliferation

1,25-dihydroxyvitamin D3 (Calcitriol) inhibits mitogen stimulated T cell proliferation by blocking the production of Interleukin-2 (IL-2). The present study was initiated to determine whether the action of calcitriol was limited only to inhibition of IL-2 production, or if it influenced other events as well. To avoid the use of lectins, thymocytes from CD-I Swiss mice were chosen, which proliferate in response to Interleukin-I (IL-I) or IL-2 without the addition of lectins. Calcitriol inhibited (80-90%) IL-I induced CD-I mouse thymocyte proliferation, whereas 25-OH-D3 was ineffective. Further addition of IL-I failed to overcome this suppression. Surprisingly, calcitriol also inhibited IL-2 induced thymocyte proliferation (60-80%). Further addition of IL-2, in the presence of calcitriol, was ineffective in enhancing thymocyte proliferation. Similar results were obtained with C57BL/10 mouse thymocytes. Additional studies excluded the possibilities that calcitriol mediated inhibition was due to calcitriol IL-2 binding or damage to thymocytes by calcitriol. Thus, calcitriol not only blocks IL-2 production, but these results strongly suggest, that it also interferes with IL-2-thymocyte interaction, which in turn results in inhibition of thymocyte proliferation.