Morton A L, Bell E B, Bolton E M, Marshall H E, Roadknight C, McDonagh M, Bradley J A
University Department of Surgery, Western Infirmary, Glasgow, Scotland.
Eur J Immunol. 1993 Sep;23(9):2078-84. doi: 10.1002/eji.1830230906.
Experimental studies of the T cell requirement for rejection of class I major histocompatibility complex (MHC)-disparate grafts have generated controversy over both the autonomy of CD8+ T cells and the mechanism whereby CD4+ T cells are able to independently mediate rejection. In this study of rejection of RT1Aa class I MHC-disparate rat cardiac and skin allografts by high-responder PVG RT1u recipients, we show that elimination of CD8+ T cells [by anti-CD8 monoclonal antibody (mAb) administration in vivo] fails to prolong graft survival, whereas partial depletion of CD4+ T cells (by anti-CD4 mAb treatment) markedly delays rejection of class I-disparate heart grafts, and marginally prolongs survival of skin grafts. Anti-CD4-treated PVG-RT1u athymic nude rats reconstituted with CD8+ T cells failed to reject class I-disparate skin grafts for several weeks and eventual rejection correlated with re-emergence of a small number of donor derived CD4+ T cells. Conversely, anti-CD8-treated nude rats reconstituted with CD4+ T cells alone rapidly rejected class I-disparate skin grafts. Passive transfer of anti-class I immune serum to anti-CD4-treated euthymic recipients promptly restored their ability to specifically reject a class I-disparate heart graft. Similarly, passive transfer of immune serum to PVG-RT1u nude rats bearing skin allografts caused destruction of class I-disparate but not third-party grafts. These results demonstrate that CD4+ T cells are both necessary and sufficient to cause rejection of class I-disparate heart and skin grafts in this model and that CD4+ T cell-dependent alloantibody plays a decisive role in effecting rejection.
关于I类主要组织相容性复合体（MHC）不相合移植物排斥反应中T细胞需求的实验研究，引发了关于CD8 + T细胞自主性以及CD4 + T细胞能够独立介导排斥反应的机制的争议。在这项由高反应性PVG RT1u受体对RT1Aa I类MHC不相合大鼠心脏和皮肤同种异体移植物进行排斥反应的研究中，我们发现，消除CD8 + T细胞（通过体内给予抗CD8单克隆抗体）并不能延长移植物存活时间，而部分清除CD4 + T细胞（通过抗CD4单克隆抗体治疗）则显著延迟I类不相合心脏移植物的排斥反应，并略微延长皮肤移植物的存活时间。用CD8 + T细胞重建的经抗CD4处理的PVG-RT1u无胸腺裸鼠在数周内未能排斥I类不相合皮肤移植物，最终的排斥反应与少量供体来源的CD4 + T细胞的重新出现相关。相反，仅用CD4 + T细胞重建的经抗CD8处理的裸鼠迅速排斥I类不相合皮肤移植物。将抗I类免疫血清被动转移至经抗CD4处理的正常胸腺受体可迅速恢复其特异性排斥I类不相合心脏移植物的能力。同样，将免疫血清被动转移至带有皮肤同种异体移植物的PVG-RT1u裸鼠会导致I类不相合而非第三方移植物的破坏。这些结果表明，在该模型中，CD4 + T细胞对于引起I类不相合心脏和皮肤移植物的排斥反应既是必要的也是充分的，并且CD4 + T细胞依赖性同种异体抗体在实现排斥反应中起决定性作用。
