MARROW GRAFT REJECTION IN ALLOGENEIC BONE MARROW TRANSPLANTATION

许多观察表明，宿主淋巴细胞， 特异性细胞毒性T细胞（CTL）可能在 介导同种异体骨髓移植排斥。在鼠模型系统中，CTL 是从亚致死剂量辐射的动物脾脏中克隆出来的， 排斥MHC不同的骨髓移植物。发现克隆的CTL是 足以影响T细胞耗尽的同种异体骨髓的排斥， 受到致命辐射的动物CTL对骨髓移植物的排斥反应 特异于骨髓细胞表达的MHC基因产物， 与单个克隆的细胞毒性特异性相关。 由于宿主CTL在分离状态下对供者骨髓移植物有排斥反应， （l）能够抑制宿主CTL反应的细胞群的植入， 和（2）体内施用抗-CD 3单克隆抗体， 通过先前的工作已经显示抑制CTL功能，进行了研究。 具有特定类型抑制活性的细胞，称为否决细胞， 可能抑制宿主排斥反应，据报道， 存在于骨髓中。IL-2增强否决权活动的能力 T细胞耗竭后骨髓中残留的抑制细胞群， 在体外和体内研究。结果表明，T 细胞耗尽的骨髓与IL-2显著增加否决活性， 通过体外试验评估，还增强了MHC- 不匹配的T细胞在体内耗尽了骨髓，否决细胞发挥了 其效果通过克隆性缺失前体CTL来实现。这种克隆消除 涉及前体CTL以及否决细胞的参与。进一步 去除T细胞的同种异体骨髓移植小鼠的移植研究 用抗CD 3单克隆抗体治疗。显著增强 观察到植入;这种对植入的影响是持久的， 抑制宿主T细胞功能和释放多种 与抗CD 3抗体体内活化T细胞相关的细胞因子 抗体的

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.