Calcitriol started in the donor, expands the population of CD4+CD25+ T cells in renal transplant recipients

Abstract

Objectives: Alloreactive T cells recognize antigens via direct and indirect pathways. The competency of costimulatory molecules on antigen-presenting cells (APC) is important. An active form of vitamin D (1,25(OH)(2)D(3), calcitriol) inhibits APC cell maturation and expression of costimulatory molecules. Herein we studied the immunosuppressive effects of calcitriol, which was started in the donors and continued in the kidney recipients.

Methods: In this prospective study, candidates for living donor renal transplantation were randomly assigned into two groups: the treatment group were prescribed calcitriol (0.5 microg/day) started in the donor 6 days before donation and continued in recipient side for 6 months after transplantation. The control group received the conventional immunosuppressive regimen, namely, cyclosporine/mycophenolate mofetil and prednisolone. In each group, a recipient blood sample was obtained before and 6 months after transplantation. Diagnostic study of the T-cell markers-CD3, CD4, and CD25-were performed with a flow cytometry technique.

Results: The mean values of CD3(+)CD4(+)CD25(+) T cells in the treatment group (four women and five men; 40.8 +/- 8.5 years) and the control group (four women and six men; 37.2 +/- 10 years) were at 14.2 +/- 4.2% and 15.4 +/- 4.5% of total peripheral lymphocytes. Six months after transplantation, these percentages increased to 29 +/- 6.3% in the treatment group and decreased to 12.1 +/- 4.5% in the controls (P<.0001). No clinical rejection was detected in either group during the study period.

Conclusion: Calcitriol started in the donors and continued in the kidney allograft recipients lead to expansion of CD4(+)CD25(+) regulatory T cells in recipients. We speculated that costimulatory deficient APC for both direct and in-direct pathways may play a role.