Ardalan M R, Maljaei H, Shoja M M, Piri A R, Khosroshahi H T, Noshad H, Argani H
Department of Nephrology, Tabriz Medical University, Tabriz.
Transplant Proc. 2007 May;39(4):951-3. doi: 10.1016/j.transproceed.2007.04.012.
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.
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.
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.
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.
同种异体反应性T细胞通过直接和间接途径识别抗原。抗原呈递细胞（APC）上共刺激分子的功能很重要。活性形式的维生素D（1,25(OH)₂D₃，骨化三醇）可抑制APC细胞成熟和共刺激分子的表达。在此，我们研究了从供体开始并在肾移植受者中持续使用的骨化三醇的免疫抑制作用。
在这项前瞻性研究中，活体供肾移植的候选者被随机分为两组：治疗组在供体捐献前6天开始服用骨化三醇（0.5微克/天），并在移植后受体方持续服用6个月。对照组接受传统免疫抑制方案，即环孢素/霉酚酸酯和泼尼松龙。每组在移植前和移植后6个月采集受体血样。采用流式细胞术对T细胞标志物CD3、CD4和CD25进行诊断研究。
治疗组（4名女性和5名男性；40.8±8.5岁）和对照组（4名女性和6名男性；37.2±10岁）中CD3⁺CD4⁺CD25⁺T细胞的平均值分别占外周血淋巴细胞总数的14.2±4.2%和15.4±4.5%。移植后6个月，治疗组这些百分比增加到29±6.3%，对照组则降至12.1±4.5%（P<0.0001）。研究期间两组均未检测到临床排斥反应。
从供体开始并在肾移植受者中持续使用的骨化三醇可导致受体中CD4⁺CD25⁺调节性T细胞扩增。我们推测直接和间接途径中缺乏共刺激的APC可能起了作用。
