Rebellato L M, Gross U, Verbanac K M, Thomas J M
Department of Surgery, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Transplantation. 1994 Mar 15;57(5):685-94. doi: 10.1097/00007890-199403150-00010.
The potent immunosuppressive action of rabbit antithymocyte globulin (RATG) in allotransplant recipients has been recognized for many years. Some of the antibody specificities and immunoregulatory effects of RATG have been described, but a comprehensive definition of RATG components has not been reported previously. In this study, we have identified 23 specificities that are consistent among different clinical RATG batches and represent the major antibody specificities in RATG. These specificities were defined by immunoprecipitation/gel electrophoresis and also antibody blocking/flow cytometry methods. Titration studies performed for semiquantitative analysis of RATG antibodies showed that the antibodies present in highest titer were directed to CD6, CD16, CD18, CD28, CD38, CD40, and CD58 (titer > 1:4000), most of which are not T cell-specific antibodies. In contrast, the RATG antibodies that persisted the longest in vivo in the plasma of rhesus monkeys transplant recipients are antibodies to CD3, CD4, CD8, CD11a, CD40, CD45, CD54, and class I. These antibodies, which are directed at signal transduction and adhesion molecules, were present during the early period of lymphocyte recovery. We suggest that the persistence of these antibodies in vivo is directly related to the prolonged anergy of circulating T cells after RATG treatment and to the unusual potency and complex tapestry of immunological effects in transplantation.
兔抗胸腺细胞球蛋白（RATG）在同种异体移植受者中具有强大的免疫抑制作用，这一点已被认识多年。RATG的一些抗体特异性和免疫调节作用已被描述，但此前尚未有关于RATG成分的全面定义报道。在本研究中，我们鉴定出了23种在不同临床RATG批次中一致的特异性，它们代表了RATG中的主要抗体特异性。这些特异性通过免疫沉淀/凝胶电泳以及抗体阻断/流式细胞术方法得以确定。对RATG抗体进行半定量分析的滴定研究表明，滴度最高的抗体针对CD6、CD16、CD18、CD28、CD38、CD40和CD58（滴度>1:4000），其中大多数并非T细胞特异性抗体。相比之下，在恒河猴移植受者血浆中体内持续时间最长的RATG抗体是针对CD3、CD4、CD8、CD11a、CD40、CD45、CD54和I类分子的抗体。这些针对信号转导和黏附分子的抗体在淋巴细胞恢复早期就已存在。我们认为，这些抗体在体内的持续存在与RATG治疗后循环T细胞的长期无反应性直接相关，也与移植中免疫效应的异常强度和复杂情况相关。
