Benham A M, Sawyer G J, Fabre J W
Transplantation Biology Unit, University of London, United Kingdom.
Transplantation. 1995 Apr 15;59(7):1028-32. doi: 10.1097/00007890-199504150-00019.
This report demonstrates for the first time that indirect T cell allorecognition of donor antigens can contribute to the effector mechanism of rejection of vascularized organ allografts. LEW (RT1(1)) rats were primed for indirect T cell allorecognition of DA (RT1av1) classical class I MHC molecules by immunization with synthetic 22-24 amino acid peptides corresponding to the alpha-helices of the RT1-A class I molecule. These rats received (DA x LEW) F1 kidney grafts that had been depleted of donor interstitial dendritic cells to minimize the direct T cell allorecognition response to the graft. The peptide-immunized rats rejected their grafts more rapidly than did control immunized rats, in terms of both graft function and survival. Moreover, the kinetics of antibody production to intact donor class I molecules after kidney transplantation was much more rapid in the peptide-immunized rats, suggesting that T cell help is the rate-limiting factor for antibody production to donor antigens in this model. It was of interest that we could not detect an antibody response to donor peptides after kidney graft rejection.
本报告首次证明，供体抗原的间接T细胞同种异体识别可促成血管化器官同种异体移植排斥反应的效应机制。通过用对应于RT1-A I类分子α螺旋的22 - 24个氨基酸合成肽进行免疫，使LEW（RT1(1)）大鼠对DA（RT1av1）经典I类MHC分子进行间接T细胞同种异体识别致敏。这些大鼠接受了已去除供体间质树突状细胞的（DA×LEW）F1肾移植，以尽量减少对移植的直接T细胞同种异体识别反应。就移植功能和存活而言，经肽免疫的大鼠比对照免疫大鼠更快地排斥其移植肾。此外，在肾移植后，经肽免疫的大鼠针对完整供体I类分子产生抗体的动力学要快得多，这表明在该模型中，T细胞辅助是针对供体抗原产生抗体的限速因素。有趣的是，在肾移植排斥后，我们未能检测到对供体肽的抗体反应。
