MARROW GRAIT FAILURE IN ALLOGENIC BONE MARROW TRANSPLANTATION

许多观察表明，宿主溶血细胞， 具体地说，细胞毒性T细胞(CTL)可能起着重要作用 在调节异基因骨髓移植排斥反应中的作用。在小鼠模型中 系统，从亚致死剂量照射小鼠的脾中克隆CTL。 排斥MHC不同骨髓移植的动物。确实是 发现克隆的CTL足以影响T细胞的排斥反应 致死照射动物体内耗尽的同种异体骨髓。这个 MHC基因特异性CTL对骨髓移植的排斥反应 由骨髓细胞表达的产物，与 单个克隆的细胞毒性特异性。尽管CTL可以 因此排斥骨髓移植，给予抗CD3抗体 到目前为止，体内的单抗还没有促进植入 在亚致死剂量照射的小鼠宿主中T细胞耗尽的骨髓。 克隆的异种特异性人CTL也直接进行了评估 它们在体内调节组织损伤的能力被发现 MHC抗原特异性介导组织损伤的研究 小鼠宿主。异种抗原识别的良好特异性 人T细胞在异种移植中的作用 组织，就像移植MHC不匹配的同种异体组织一样， 特定的组织抗原以及因此的组织分型可以 是一个相关的考虑因素。人类CTL的产生已经被 其中表征的和某些基本的细胞相互作用 一代人的身份已经确定。此外，用于 抗CD2单抗的封闭作用 (绵羊红细胞受体)、CD8和CD18(LFA-1)分子 在人CTL表面的表达已被研究过。 结果表明，抗CD2抗体对小鼠肝细胞的抑制作用不明显。 在没有目标单元格的情况下发生，与 解释该抗体通过以下途径发挥封闭作用 干扰CD2配体的相互作用。然而，结果是 抗CD8和抗CD18的单抗表明 这些药物的抑制作用不能用简单的 破坏T细胞受体-靶细胞配体的相互作用。

A number of observations have suggested that host lymohocytes, specifically cytotoxic T cells (CTL) may play a significant role in mediating allogeneic marrow graft rejection. In a murine model system, CTL were cloned from the spleens of sublethally irradiated animals which had rejected MHC disparate marrow grafts. It was found that cloned CTL were sufficient to effect rejection of T cell depleted allogeneic marrow in lethally irradiated animals. The rejection of marrow grafts by CTL was specific for the MHC gene products expressed by the marrow cells and correlated with the cytotoxic specificity of the individual clones. Although CTL can therefore reject marrow grafts, the administration of anti-CD3 monoclonal antibody in vivo has to date not enhanced engraftment of T cell depleted marrow in sublethally irradiated murine hosts. Cloned xenospecific human CTL were also directly evaluated for their ability to mediate tissue damage in vivo and were found to mediate tissue injury with specificity for MHC antigens of the murine host. The fine specificity of xeno-antigen recognition by human T cells suggests that in transplantation of xenogeneic tissue, as in transplantation of MHC mismatched allogeneic tissue, the particular tissue antigens, and therefore tissue typing, may be a relevant consideration. The generation of human CTL has been characterized and certain essential cellular interactions in that generation have been identified. In addition, the mechanisms for the blocking effects of monoclonal antibodies specific for the CD2 (sheep red blood cell recoptor), CD8, and CD18 (LFA-1) molecules expressed on the surface of human CTL have been investigated. Results indicate that the inhibition by anti-CD2 antibody did not occur in the absence of target cells, consistent with the interpretation that this antibody exerts its blocking effect by interfering with a CD2 ligand interaction. However, results with anti-CD8 and anti-CD18 monoclonal antibodies indicated that inhibition by these agents could not be explained by simple disruption of a T cell receptor-target cell ligand interaction.