Induction of hyperacute rejection of skin allografts by CD_8^+ Lymphoats

第二集排斥反应通常被认为是一种主要由体液细胞毒抗体介导的现象，尽管有一些不一致的数据。在已报道的实验中，我们利用了与移植细胞免疫正常发育相反的缺乏特异性细胞毒性同种抗体的优点，在两种动物模型中，T细胞和B细胞功能完全缺陷的重组激活基因缺失(RAG)小鼠和嵌合(BALB/c*CBA)小鼠。在所有超免疫嵌合小鼠中均未检测到抗B细胞毒抗体，但B6皮肤移植发生了加速排斥反应：移植物存活8.6×0.5天(D)，与相同超免疫程序的CBA对照小鼠的8.9×0.8 d相当，显著短于未高免疫(BALB/c CBA)嵌合体小鼠(11.6±0.5 d)或未高免疫CBA对照小鼠(12.1±0.6 d)。高滴度抗B6 Cy…高免CBA对照组小鼠血清中有更多的TO毒性抗体。进行了传质实验。然后，将B6皮肤移植到受体小鼠身上。单纯照射、照射+血清或照射+CD4+T细胞组小鼠移植物存活时间均在14d以上。照射+全脾细胞组、照射+T细胞组和照射+CD8+T细胞组小鼠的存活时间明显缩短(8.9×0.8d)。当RAG小鼠接受预敏的[TCD_4~+、T_8~+或T细胞]或超敏B6小鼠血清时，皮肤移植物的加速排斥反应仅在注射敏感的TCD_8~+细胞组(12.0±0.68天)和注射T细胞组(14.0±0.84天)发生，而注射TCD_4~+细胞(16.5±0.11天)的小鼠皮肤移植物发生加速排斥反应的时间较长。因此，在嵌合小鼠模型中，T细胞，特别是CD8+亚群，似乎是在缺乏抗供体抗体的情况下导致第二集排斥反应的原因。这些致敏的CD8+T细胞也可能在正常小鼠中发挥重要作用。较少

Second-set rejection is generally regarded as a phenomenon mainly mediated by humoral cytotoxic antibodies, although a few discordant data have been presented. In the reported experiments, we have taken advantage of the absence of production of specific cytotoxic alloantibodies contrasting with normal development of transplantation cellular immunity, in 2 models of animals the recombination activation gene deletion (RAG) mice wich are fully defective in any functionnal T cell and B cell, and the chimeric (BALB/c * CBA) mice. Anti-B cytotoxic antibodies were not detectable in any of hyperimmunized chimeric mice, yet accelerated rejection of B6 skin transplant occurred : graft survival of 8.6 * 0.5 days (d), comparable to the 8.9 * 0.8 d survival in CBA control mice subjected to the same hyperimmunization procedure, and significantly shorter than in non-hyperirnmunized (BALB/c CBA) chimeras (11.6 * 0.5 d) or in non-hyperimmunized CBA control mice (12.1 * 0.6 d). High titers of anti-B6 cy … More totoxic antibodies were present in the serum of hyperimmunized CBA control mice. Transfer experiments were carried out. The recipient mice were then grafted with B6 skin. The graft survival was over 14 d in mice treated with irradiation alone, with irradiation + serum, or with irradiation + CD4+ T cells. It was significantly shorter in mice treated with irradiation + whole spleen cells, with irradiation + T cells, or with irradiation +CD8+ T cells (8.9 * 0.8 d). When RAG mice recieved pre-sensitesed [TCD4+ or TCD8+ or T cells] or serum from hyperinununised B6 mice, accelerated rejection of the skin grafts was occured only in the groups of mice injected with sensitesed TCD8+ cells or T cells (12.0 * 0.68 d and 14.0 * 0.84 d) respectively this delay is longuer in mice injected with TCD4+ cells (16.5 * 0.11d) The latter cells have been able to transfer the property of inducing accelerated rejection into naive mice. T cells, and especially the CD8+ subset, thus appear to be responsible for the second-set rejection in the absence of anti-donor antibodies, in the model of chimeric mice. These sensitized CD8+ T cells are likely to also play an important role in normal mice. Less