MARROW GRAFT REJECTION IN ALLOGENEIC BONE MARROW TRANSPLANTATION

许多观察表明，宿主淋巴细胞， 具体地说，细胞毒性T细胞(CTL)在 调节同种异体骨髓移植排斥反应。在小鼠模型系统中，CTL 是从亚致死剂量照射的动物的脾中克隆出来的 排斥MHC完全不同的骨髓移植。研究发现，克隆的CTL是 足以使T细胞耗尽的异基因骨髓发生排斥反应 受到致命辐射的动物。CTL对骨髓移植的排斥反应为 针对骨髓细胞表达的MHC基因产物和 与单个克隆的细胞毒特异性相关。 因为隔离的宿主CTL可以排斥供者的骨髓移植，所以对 能够抑制宿主CTL反应的(L)细胞群的植入， (2)体内注射抗CD3单抗。 由前人的工作已显示出抑制CTL的功能，都进行了研究。 具有特定类型的抑制活性的细胞，称为否决权细胞， 可能会抑制寄主排斥反应，据报道是 存在于骨髓中。LL-2增强否决权活性的能力 T细胞耗尽后残留在骨髓中的抑制性细胞群 体外和体内研究。研究发现，T细胞的孵化 细胞耗尽的骨髓与IL-2一起显著增加否决权活性，因为 通过体外试验进行评估，并增强MHC- 体内不匹配的T细胞耗尽了骨髓，否决权细胞发挥了作用 它们通过克隆性删除前体CTL而发挥作用。这样的克隆消除 涉及前体CTL和否决权细胞的参与。在进一步的 T细胞耗竭异基因骨髓植入宿主小鼠的实验研究 用抗CD3单抗治疗。显著增强了 观察到了嫁接；这种对嫁接的影响是持久的和适当的 抑制宿主T细胞功能，释放多个 与抗CD3抗体体内激活T细胞相关的细胞因子 抗体。

A number of observations have suggested that host lymphocytes, 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. Because host CTL in isolation could reject donor marrow grafts, effects on engraftment by (l) cell populations able to suppress host CTL responses, and (2) the administration of anti-CD3 monoclonal antibody in vivo, which by previous work had been shown to suppress CTL function, were studied. Cells with a specific type of suppressor activity, termed veto cells, which might suppress host rejection responses, have been reported to be present in marrow. The ability of lL-2 to enhance the activity of veto suppressor cell populations remaining in marrow after T cell depletion was investigated in vitro and in vivo. It was found that the incubation of T cell depleted marrow with IL-2 significantly increased veto activity as assessed by in vitro assays and also enhanced engraftment of MHC- mismatched, T cell depleted marrow in vivo, and that veto cells exerted their effect by clonal deletion of precursor CTL. Such clonal elimination involved participation by precursor CTL as well as veto cells. In further studies of engraftment of T cell depleted allogeneic marrow, host mice were treated with anti-CD3 monoclonal antibody. Marked enhancement of engraftment was observed; this effect on engraftment was enduring and due to suppression of host T cell function and to the release of multiple cytokines associated with in vivo activation of T cells by anti-CD3 antibody.