不同诱导治疗对肾移植受者单核样髓系抑制性细胞的影响  

Effect of induction therapy regimens on monocytic myeloid-derived suppressor cells in kidney transplantation recipients

作　　者：蒋一航 王浩舟[2] 杨晶[1] 封素娟[1] 张小东[1] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿外科,北京100020 [2]首都医科大学研究生院

出　　处：《中华器官移植杂志》2016年第7期385-391,共7页Chinese Journal of Organ Transplantation

基　　金：北京市医院管理局重点医学专业发展计划（ZYLX201408）

摘　　要：目的研究常用诱导药物对于肾移植受者外周血单核样髓系抑制性细胞（M-MDSCs）的影响，并探讨其相关机制。方法入组受者分别接受兔抗人胸腺细胞球蛋白（rA]晤）或巴利昔单抗诱导治疗，术后采用他克莫司＋吗替麦考酚酯＋皮质激素预防排斥反应。肾移植术前及术后1周、2周、1个月、2个月、3个月检测外周血CDllb＋CD33＋HLA-DR—CD14＋CD15-M-MDSCs数量和r干扰素（IFN-7）、白细胞介素2（IL-2）、IL-4、IL-6等可影响MDSCs扩增的细胞因子浓度。结果47例受者人组，其中rATG组29例，巴利昔单抗组18例。术后2个月和3个月时，rATG组受者M-MDscs百分数显著增加，高于巴利昔单抗组。2个月时，rATG组受者M-MIXSCs百分数为（5．5±2．8）％，巴利昔单抗组受者M-MIXSCs百分数为（3．8±1．6）％，P〈0．001。3个月时，rATG组受者M-MDSCs百分数为（7．0±3．1）％，巴利昔单抗组受者M-MDSCs百分数为（4．1±2．3）％，P〈0．001。两组间M-MDSCs绝对数比较，差异均无统计学意义。术后2周、1个月时两组的IL-2、IL-4比较，差异有统计学意义；2周时，PIL-2=0．032，PIL-4=0．019；1个月时，PIL-2=0．024，PIL-4〈0．001。结论rATG清除淋巴细胞过程中导致IL-2、IL-4释放，促进M-MI）SCs扩增，发挥协同免疫抑制作用，可能有利于免疫耐受的诱导。Objective To investigate the effects of commonly used inductive agents on peripheral blood monocytic myeloid-derived suppressor cells （M-MDSCs） in renal transplantation recipients and to discuss their possible mechanism. Methods The enrolled patients reeeived rabbit anti-thymocyte globulin （rATG） or basiliximab for induction therapy, with the maintenance immunosuppressive regimen of tacrolimus, mycophenolate mofetil and steroid. The number of CD11b＋ CD33＋ HLA-DR - CD14 ＋ CD15 - M-MDSCs and cytokine levels in peripheral blood, including interferon-γ （IFN-γ）, interleukin-2 （IL-2）, IL-4 and IL-6, were measured by flow cytometry before and 1 week, 2 weeks, 1 month, 2 months, 3 months after operation. Results A total of 47 recipients （29 given rATG 29, and 18 given basiliximab） were included in this study. Compared to the patients with basiliximab, a-significant increase in the frequency of M-MDSCs was observed in the rATG group at 2nd month after operation （5. 5% ＋ 2. 8% vs. 3. 8% ＋ 1.6%, P〈0. 001） and at 3rd month after operation （7. 0% ＋ 3. 1%vs. 4. 1% ＋ 2. 3%, P^O. 001）, while there was no significant difference in the cell number between the two groups. In the cytokine detection, levels of IL-2 and IL-4 in the rATG-treated recipients were significantly higher at 2nd weekpostoperation （PIL-2 = 0. 032, and PIL-4 = 0. 019）and 1st month postoperation （PIL-2 = 0. 024, PIL-4 d0. 001） than the basiliximab group.Conclusions ATG promotes the expansion of M-MI）SCs, which is associated with the secretion of IL-2 and IL-4 due to the lymphocytes depletion. The synergistic immunosuppressive effect may contribute to the induction of immune tolerance.

关 键 词：肾移植 诱导治疗 免疫耐受 髓系抑制性细胞 

分 类 号：R699.2[医药卫生—泌尿科学]