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Full activation of T cells requires 2 distinct but synergistic signals. The first is the T-cell antigen receptor, which is antigen specific, and the second is activation of co-stimulatory signals. Active vitamin D (1, 25-dihydroxyvitamin D3) decreases T-cell activation and proliferation, inhibits differentiation and maturation of dendritic cells, and induces tolerogenic dendritic cells. These immunoregulatory effects may be due, at least in part, to changes in cytokine secretion and expression of co-stimulatory molecules. The use of active vitamin D has been reported to improve allograft survival, decelerate loss of allograft function, and prevent acute rejection. This study was conducted to assess the effect of active vitamin D on the expression of co-stimulatory molecules and HLA-DR in renal transplant recipients.In this prospective study, we enrolled 24 renal transplant recipients who had undergone a transplant 6 to 18 months earlier, had stable allograft function, and were without episodes of allograft dysfunction or febrile illness in the previous 2 months. Participants were administered oral calcitriol 0.5 micrograms daily for 4 weeks. Expression of HLA-DR, CD28, CD86, and CD40 in peripheral blood leukocytes was assessed by flow cytometry before and after calcitriol administration.Compared to baseline levels, expression of HLA-DR decreased by 16.8%; expression of CD28, by 30%; of CD40, by 31.2%; and of CD86, by 36.7%.In renal transplant recipients, decreased expression of co-stimulatory and HLA-DR molecules occurred after treatment with active vitamin D. Such changes may be involved in increasing allograft survival.