Wang J, Geissler E K, Fechner J H, Burlingham W J, Knechtle S J
Department of Surgery, University of Wisconsin, Madison 53792.
J Surg Res. 1994 Jul;57(1):150-5. doi: 10.1006/jsre.1994.1123.
Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains soluble MHC class I antigen, is able to neutralize the effect of anti-donor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rejection. Seven of 10 recipients of hyperimmune serum (HyS), derived from Lewis rats (RT1l) following 3 ACI (RT1a) skin grafts, developed hyperacute or accelerated rejection. Intravenous injection of ACI serum prior to the HyS administration prevented hyperacute rejection in all recipients tested. When third-party (Wistar-Furth, RT1u) serum was given to Lewis rats injected with HyS, hyperacute rejection was not abrogated. When examining the mechanism of this effect, a simple antibody blocking phenomenon was found to be unlikely since flow cytometry analysis showed that ACI serum needed to be present at > or = 256-fold excess compared to HyS to block anti-ACI antibody binding to RT1.Aa+cells by 50%. We tested whether the RT1.Aa class I antigen in ACI serum had other biologic properties that resulted in the prolonged graft survival. However, removal of RT1.Aa antigen from ACI serum prior to use in the passive transfer model did not abrogate the graft prolongation observed previously. These data suggest that components of donor serum other than MHC class I antigen may be useful for preventing the antibody-mediated component of hyperacute rejection.
由于存在超急性排斥反应的风险，目前尚无已知的治疗方法，因此预先致敏的受者进行心脏和肾脏移植仍然是禁忌的。我们测试了含有可溶性MHC I类抗原的供体血清是否能够中和受者体内抗供体抗体的作用，并预防超急性或加速性排斥反应。采用大鼠被动免疫模型来测试抗供体抗体在超急性排斥反应中的作用。10只接受了来自Lewis大鼠（RT1l）在3次ACI（RT1a）皮肤移植后产生的超免疫血清（HyS）的受者中，有7只发生了超急性或加速性排斥反应。在给予HyS之前静脉注射ACI血清可预防所有受试受者发生超急性排斥反应。当将第三方（Wistar-Furth，RT1u）血清给予注射了HyS的Lewis大鼠时，超急性排斥反应并未消除。在研究这种效应的机制时，发现不太可能是简单的抗体阻断现象，因为流式细胞术分析表明，与HyS相比，ACI血清需要以≥256倍的过量存在，才能使抗ACI抗体与RT1.Aa +细胞的结合被阻断50%。我们测试了ACI血清中的RT1.Aa I类抗原是否具有其他生物学特性，从而导致移植存活时间延长。然而，在用于被动转移模型之前从ACI血清中去除RT1.Aa抗原并不能消除先前观察到的移植存活时间延长的现象。这些数据表明，供体血清中除MHC I类抗原以外的成分可能有助于预防超急性排斥反应中抗体介导的成分。
