Milton A D, Spencer S C, Fabre J W
Transplantation. 1986 Oct;42(4):337-47. doi: 10.1097/00007890-198610000-00002.
We have previously reported 5-30-fold increases in the expression of class I and class II major histocompatibility complex (MHC) antigens in rejecting heart and kidney allografts in the DA-to-PVG rat strain combination. We examine here the effects of immunosuppression with cyclosporine on the induction of donor class I and class II MHC antigens in heart and kidney allografts in this strain combination. Immunohistological studies and quantitative absorption analyses using monoclonal antibodies and assay systems specific for donor class I and class II MHC antigens were used throughout. Heart allografts in cyclosporine-treated rats were examined on day 3,5,7,9,11, and 14 after transplantation, and kidney allografts in cyclosporine-treated rats were examined at day 7. In addition, untreated heart and kidney isografts were studied at days 1,3,5, and 7 after grafting. Immunohistological studies on frozen sections showed that cyclosporine-treated heart and kidney allografts showed no induction of class II MHC antigens, in contrast to untreated heart and kidney allografts. Class I MHC antigen induction did occur in spite of cyclosporine-therapy, but at levels lower than those seen in untreated allografts. Moreover, the pattern and degree of class I induction in the cyclosporine-treated allografts resembled very closely those seen in isografts, and so this induction was, in all probability, a consequence of the transplantation procedure rather than of specific immune responses. We also noted, in the cyclosporine-treated heart allografts, that all donor interstitial dendritic cells had disappeared and been replaced by recipient interstitial dendritic cells by the end of the second week after grafting. In addition, there was no reduction in the class II antigen content of kidney allografts treated for 7 days with cyclosporine. The absence of class II antigen induction in allografts where rejection is effectively suppressed with cyclosporine might be of clinical value in the differential diagnosis between rejection and cyclosporine toxicity in renal transplantation, and between active and inactive cellular infiltrates in heart transplantation.
我们先前曾报道，在DA到PVG大鼠品系组合中，排斥反应中的心脏和肾脏同种异体移植中，I类和II类主要组织相容性复合体（MHC）抗原的表达增加了5至30倍。在此，我们研究了环孢素免疫抑制对该品系组合中心脏和肾脏同种异体移植中供体I类和II类MHC抗原诱导的影响。整个实验过程中均使用了免疫组织学研究以及使用针对供体I类和II类MHC抗原的单克隆抗体和检测系统进行的定量吸收分析。对环孢素处理的大鼠的心脏同种异体移植在移植后第3、5、7、9、11和14天进行检查，对环孢素处理的大鼠的肾脏同种异体移植在第7天进行检查。此外，对未处理的心脏和肾脏同基因移植在移植后第1、3、5和7天进行研究。对冰冻切片的免疫组织学研究表明，与未处理的心脏和肾脏同种异体移植相反，环孢素处理的心脏和肾脏同种异体移植未显示II类MHC抗原的诱导。尽管进行了环孢素治疗，I类MHC抗原诱导仍会发生，但水平低于未处理的同种异体移植。此外，环孢素处理的同种异体移植中I类诱导的模式和程度与同基因移植中所见的非常相似，因此这种诱导很可能是移植过程的结果，而不是特异性免疫反应的结果。我们还注意到，在环孢素处理的心脏同种异体移植中，到移植后第二周结束时，所有供体间质树突状细胞均已消失，并被受体间质树突状细胞所取代。此外，用环孢素处理7天肾同种异体移植的II类抗原含量没有降低。在环孢素有效抑制排斥反应的同种异体移植中，II类抗原诱导的缺失可能在肾移植中排斥反应与环孢素毒性的鉴别诊断以及心脏移植中活跃与不活跃细胞浸润的鉴别诊断中具有临床价值。
