Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy
Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy
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DOI：
10.1093/ndt/gfr693
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发表时间：
2012-06-01
影响因子：
6.1
通讯作者：
Viklicky, Ondrej
中科院分区：
文献类型：
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作者：
Krystufkova, Eva;Sekerkova, Alena;Viklicky, Ondrej
背景调节性T细胞被认为下调同种免疫应答。这项前瞻性开放研究的目的是评估不同诱导剂对肾移植患者外周血调节性T细胞的影响，并分析其与短期移植物结局的相关性。采用流式细胞术检测71例肾移植受者术后0、7、14、21、28、60和90天外周血中调节性和效应性T细胞数。患者接受基于钙调神经磷酸酶的三联免疫抑制治疗，包括多克隆兔抗胸腺细胞球蛋白（rATG，n = 28）、巴利昔单抗、抗CD 25单克隆抗体（n = 18）或无诱导（对照组，n = 25）。流式细胞术数据与排斥反应发生率相关。与对照组相比，在移植后第14天的所有时间点，在rATG组中观察到CD 4（+）T细胞中的CD 4（+）CD 25（+）FoxP 3（+）调节性T细胞扩增（P < 0.001）。在移植后7-60天，在巴利昔单抗治疗的患者中观察到Treg频率显著降低（P < 0.001），同时CD 4（+）CD 25（低/-）FoxP 3（+）群体短暂增加。活检证实的急性排斥反应发生在对照组的16.7%，rATG组的10.7%和巴利昔单抗组的11.1%。巴利昔单抗诱导后无排斥反应的患者CD 4（+）FoxP 3（+）/CD 8（+）CD 45 RA（+）CD 62 L（-）比值明显升高（P < 0.01）。在这项研究中，rATG诱导治疗与调节细胞的扩增相关。持续的高CD 4（+）FoxP 3（+）/Teff比值与巴利昔单抗诱导后无排斥反应相关。
Background. Regulatory T cells have been suggested to down-regulate the alloimmune response. The aim of this prospective open study was to evaluate the effects of different inductive agents on peripheral blood regulatory T cells in kidney transplant patients and to analyse their association with short-term graft outcome.Methods. Regulatory and effector T cell numbers in peripheral blood were determined by flow cytometry in 71 prospectively followed kidney transplant recipients at postoperative day 0, 7, 14, 21, 28, 60 and 90. Patients were treated with a calcineurin inhibitor-based triple immunosuppression with polyclonal rabbit anti-thymocyte globulin (rATG, n = 28), basiliximab, the anti-CD25 monoclonal antibody (n 18) or without induction (controls, n 25). Flow cytometry data were correlated to rejection incidence.Results. Compared to controls, CD4(+)CD25(+)FoxP3(+) regulatory T-cell expansion among CD4(+) T cells was noticed in the rATG group at all post-transplant time-points by Day 14 (P < 0.001). A significant decrease in Treg frequency (P < 0.001) and concurrently a transient increase of CD4(+)CD25(low/-)FoxP3(+) population were observed in basiliximab-treated patients 7-60 days post-transplantation. Biopsy-proven acute rejection occurred in 16.7% of controls, 10.7% of the rATG group and in 11.1% of the basiliximab group. Higher CD4(+)FoxP3(+)/CD8(+)CD45RA(+)CD62L(-) ratios were observed repeatedly in those patients after basiliximab induction who were rejection free (P < 0.01).Conclusions. In this study, the rATG induction therapy was associated with an expansion of regulatory cells. Sustained high CD4(+)FoxP3(+)/Teff ratios were associated with the absence of rejection after basiliximab induction.