INHIBITORY EFFECT OF 1-ALPHA,25-DIHYDROXYVITAMIN D-3 ON ALLOGENEIC LYMPHOCYTE STIMULATION AND LANGERHANS CELL MATURATION

1 alpha,25-Dihydroxyvitamin D-3 (calcitriol) has been shown to inhibit the proliferation of peripheral blood mononuclear cells induced by al logeneic Langerhans cells in a human mixed epidermal cell lymphocyte r eaction. The potent antigen-presenting function of Langerhans cells is gained during culture, We tried to dissect the effect of calcitriol o n lymphocyte proliferation and Langerhans cell maturation in a murine mixed epidermal cell lymphocyte reaction using unfractioned epidermal cells as a source for Langerhans cells. First, calcitriol was added up on setup of the mixed epidermal cell lymphocyte reaction using culture d epidermal cells as antigen-presenting cells, and this was found to i nhibit the proliferation of lymphocytes in a time- and concentration-d ependent manner. When calcitriol was added only during preculture of f reshly isolated epidermal cells, the subsequent mixed epidermal cell l ymphocyte reaction was also inhibited, In addition, the growth of kera tinocytes and the production of granulocyte/macrophage colony-stimulat ing factor during preculture of epidermal cells was completely inhibit ed, Supplementation with this growth factor only partially restored th e proliferative response of lymphocytes. These results suggest that ca lcitriol inhibits both the alloantigen-driven stimulation of naive T c ell and Langerhans cells maturation, Further experiments with purified Langerhans cells are required to elucidate the mechanism of action of calcitriol on Langerhans cell maturation.