Chu Z-Q, Ji Q
Tianjin First Central Hospital, Abdominal Imaging and Transplant Unit, Tianjin, China.
Transplant Proc. 2013 Jan-Feb;45(1):153-6. doi: 10.1016/j.transproceed.2012.07.145.
To achieve a true state of allo-tolerance is one of the ultimate goals in transplantation. Many studies suggest that CD4(+)CD25(high) T regulatory cells (Tregs) have a crucial role to down-regulate the immune response to allo-antigens. In this study, we investigated the possible influence of immunosuppressive therapy, including sirolimus (SRL) and calcineurin inhibitors (CNIs, tacrolimus, or cyclosporine), on the level of Tregs in renal allograft recipients.
We assessed 88 renal transplant recipients with stable renal function for at least 2 years, dividing them into 2 groups: SRL-treated (n = 28) or CNIs-treated (n = 29 tacrolimus and n = 31 cyclosporine). Thirty-eight age-matched healthy subjects (HS) served as normal controls. We examined the expression of CD4, CD25, and forkhead box p3 (Foxp3) in peripheral blood mononuclear cells. Flow cytometry was performed with data analysis using Cell Quest software. The 5-year graft survivals were correlated with Tregs content.
CNIs significantly decreased the percentage of Tregs compared with the HS and SRL groups (P < .01). The percentage of Tregs in the SRL group was not significantly different from that among HS. The ratio of CD4(+)CD25(high)Tregs to CD4(+) T cells was 0.88% (0.28-1.42%), 1.15% (0.57-1.48%), and 0.21% (0.11-0.29%) among the SRL, HS, and CNIs cohorts respectively (SRL vs CNIs, P = .000165; SRL vs HS, P = .258; CNIs vs HS, P = .00030). Foxp3 was expressed in >95% of CD4(+)CD25(high) T cells versus <20% among CD4(+)CD25(low) T cells and not at all in CD4(+)CD25(-) T cells. Five-year graft survivals showed no difference between the 2 cohorts (P > .05), and was not correlated with the level of CD4(+)CD25(high) T cells.
Various immunosuppressive therapies may show different roles in tolerance induction. The present findings suggest that SRL facilitates the induction of CD4(+)CD25(high) T cells, whereas CNIs hamper their development. Graft success for 5 years did not correlate with the level of these putative regulatory cells.
实现真正的同种异体耐受状态是移植领域的最终目标之一。许多研究表明，CD4(+)CD25(高)调节性T细胞（Tregs）在下调对同种异体抗原的免疫反应中起关键作用。在本研究中，我们调查了免疫抑制疗法，包括西罗莫司（SRL）和钙调神经磷酸酶抑制剂（CNIs，他克莫司或环孢素）对肾移植受者体内Tregs水平的可能影响。
我们评估了88例肾功能稳定至少2年的肾移植受者，将他们分为2组：SRL治疗组（n = 28）或CNIs治疗组（n = 29例他克莫司和n = 31例环孢素）。38例年龄匹配的健康受试者（HS）作为正常对照。我们检测了外周血单个核细胞中CD4、CD25和叉头框p3（Foxp3）的表达。使用Cell Quest软件进行流式细胞术并进行数据分析。将5年移植存活率与Tregs含量进行相关性分析。
与HS组和SRL组相比，CNIs显著降低了Tregs的百分比（P <.01）。SRL组中Tregs的百分比与HS组之间无显著差异。SRL组、HS组和CNIs组中CD4(+)CD25(高)Tregs与CD4(+) T细胞的比例分别为0.88%（0.28 - 1.42%）、1.15%（从0.57 - 1.48%）和0.21%（0.11 - 0.29%）（SRL组与CNIs组比较，P = 0.000165；SRL组与HS组比较，P = 0.258；CNIs组与HS组比较，P = 0.00030）。Foxp3在>95%的CD4(+)CD(25高)T细胞中表达，而在CD4(+)CD25(低)T细胞中<20%表达，在CD4(+)CD25(-)T细胞中完全不表达。两组的5年移植存活率无差异（P >.05），且与CD4(+)CD25(高)T细胞水平无关。
各种免疫抑制疗法在诱导耐受方面可能发挥不同作用。目前的研究结果表明，SRL促进CD4(+)CD25(高)T细胞的诱导，而CNIs则阻碍其发育。5年移植成功与否与这些假定的调节性细胞水平无关。
