Laboratory of Immunology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
Hum Immunol. 2010 May;71(5):442-50. doi: 10.1016/j.humimm.2010.01.022. Epub 2010 Feb 13.
In organ transplantation, the immunosuppression withdrawal leads, in most cases, to rejection. Nonetheless, a special group of patients maintain stable graft function after complete withdrawal of immunosuppression, achieving a state called "operational tolerance." The study of such patients may be important to understand the mechanisms involved in human transplantation tolerance. We compared the profile of CD4(+)CD25(+)Foxp3(+) T cells and the signaling pathways IL-6/STAT3 (signal transducers and activators of transcription) and IL-4/STAT6 in peripheral blood mononuclear cells of four kidney transplant groups: (i) operational tolerance (OT), (ii) chronic allograft nephropathy (CR), (iii) stable graft function under standard immunosuppression (Sta), (iv) stable graft function under low immunosuppression, and (v) healthy individuals. Both CR and Sta displayed lower numbers and percentages of CD4(+)CD25(+)Foxp3(+) T cells compared with all other groups (p < 0.05). The OT patients displayed a reduced activation of the IL-4/STAT6 pathway in monocytes, compared with all other groups (p < 0.05). The lower numbers of CD4(+)CD25(+)Foxp3(+) T cells observed in CR individuals may be a feature of chronic allograft nephropathy. The differential OT signaling profile, with reduced phosphorylation of STAT6, in monocytes' region, suggests that some altered function of STAT6 signaling may be important for the operational tolerance state.
在器官移植中，免疫抑制的撤除在大多数情况下会导致排斥反应。然而，有一小部分患者在完全撤除免疫抑制剂后，仍能保持移植物功能的稳定，达到一种被称为“免疫耐受”的状态。对这些患者的研究可能对理解人类移植耐受的机制很重要。我们比较了四组肾移植患者外周血单个核细胞中 CD4(+)CD25(+)Foxp3(+)T 细胞的特征以及 IL-6/STAT3（信号转导和转录激活因子）和 IL-4/STAT6 信号通路：（i）免疫耐受（OT），（ii）慢性移植肾肾病（CR），（iii）标准免疫抑制下稳定的移植物功能（Sta），（iv）低免疫抑制下稳定的移植物功能，和（v）健康个体。与其他所有组相比，CR 和 Sta 组的 CD4(+)CD25(+)Foxp3(+)T 细胞数量和比例都较低（p < 0.05）。与其他所有组相比，OT 患者的单核细胞中 IL-4/STAT6 通路的激活程度降低（p < 0.05）。CR 患者中观察到的 CD4(+)CD25(+)Foxp3(+)T 细胞数量减少可能是慢性移植肾肾病的一个特征。OT 患者在单核细胞区域中 STAT6 信号的磷酸化程度降低，提示 STAT6 信号的某些改变功能可能对免疫耐受状态很重要。
