1-ALPHA,25-DIHYDROXYVITAMIN D3 (CALCITRIOL) INDUCES APOPTOSIS IN STIMULATED T-CELLS THROUGH AN IL-2 DEPENDENT MECHANISM

The steroid hormone 1 alpha,25-dihydroxyvitamin D3 (calcitriol) has be en shown to inhibit PHA-induced T-cell proliferation, In the present w ork we show that calcitriol caused a concentration-dependent decrease in the viability of PHA stimulated but not unstimulated T lymphocytes. Under microscopy, nonviable cells exhibit classic features of program med cell death or apoptosis. In addition, the same concentration of ca lcitriol induces a blockage in the G1 phase of T cell cycle and decrea sed secretion of IL-2, which was correlated with the extent of apoptos is. Thus, addition of exogenous IL-2 reverted both the cell cycle bloc k and the apoptotic cell death induced by calcitriol, This data indica tes that calcitriol induced apoptotis in PHA-stimulated T cell, and su ggests that this action is mediated through suppression of IL-2 secret ion. (C) 1996 Academic Press Limited