Zhao T, Yang C, Qiu Y, Xue Y, Zhao Z, Song D, Qiu Y, Ma Z, Yang B, Xu M, Rong R, Zhu T
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Transplant Proc. 2013 Jan-Feb;45(1):148-52. doi: 10.1016/j.transproceed.2012.06.067.
Sirolimus-based regimens have recently been introduced as nephron-sparing strategies to avoid the calcineurin inhibitors-induced nephrotoxicity.
To investigate the different effects of these 2 immunosuppressants on CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) and the newly defined subsets of FoxP3(+) T cells, including CD45RA(-)FoxP3(lo) cytokine-secreting T cells (csT cells), CD45RA(-)FoxP3(hi) activated Treg (aTregs), and CD45RA(+)FoxP3(+) resting Treg (rTregs), 52 cases of renal transplant recipients who have received a maintenance immunosuppressive regimen comprised either cyclosporine (n = 34) or sirolimus (n = 18) were collected and proportion of Tregs and each subset of FoxP3(+) T cells in peripheral blood was detected by flowcytometry.
Sirolimus significantly prompted the proportion of Tregs (5.92 ± 0.40 vs 2.19 ± 0.18; P < .001) and both of the CD45RA-negative subsets, including csT cells (4.92 ± 0.50 vs 1.83 ± 0.18; P < .001) and aTregs (1.04 ± 0.15 vs 0.23 ± 0.05; P < .05) when compared with cyclosporine. However, the rTregs were not remarkably affected (0.36 ± 0.09 vs 0.79 ± 0.28; P = .063).
Sirolimus plays its immune regulatory role in renal transplantation partly by increasing the proportion of Tregs. However, the increasing of both pro- and anti-inflammatory subsets of FoxP3(+) T cells also indicates the potential compromising of the effects of sirolimus on immune regulation.
基于西罗莫司的治疗方案最近已被引入作为保留肾单位的策略,以避免钙调神经磷酸酶抑制剂诱导的肾毒性。
为研究这两种免疫抑制剂对CD4(+)CD25(hi)FoxP3(+)调节性T细胞(Tregs)以及新定义的FoxP3(+)T细胞亚群(包括CD45RA(-)FoxP3(lo)细胞因子分泌性T细胞(csT细胞)、CD45RA(-)FoxP3(hi)活化Treg(aTregs)和CD45RA(+)FoxP3(+)静息Treg(rTregs))的不同影响,收集了52例接受环孢素(n = 34)或西罗莫司(n = 18)维持免疫抑制方案的肾移植受者,并通过流式细胞术检测外周血中Tregs及FoxP3(+)T细胞各亚群的比例。
与环孢素相比,西罗莫司显著提高了Tregs的比例(5.92±0.40对2.19±0.18;P<.001)以及两个CD45RA阴性亚群的比例,包括csT细胞(4.92±0.50对1.83±0.18;P<.001)和aTregs(1.04±0.15对0.23±0.05;P<.05)。然而,rTregs未受到显著影响(0.36±0.09对0.79±0.28;P = .063)。
西罗莫司在肾移植中发挥免疫调节作用部分是通过增加Tregs的比例。然而,FoxP3(+)T细胞促炎和抗炎亚群的增加也表明西罗莫司对免疫调节作用可能存在损害。