GRAFT REJECTION--CELLULAR & CYTOKINE REGULARION OF TRANSPLANTATION RESPONSES

许多观察表明，宿主淋巴细胞， 特异性细胞毒性T细胞（CTL）在 介导同种异体骨髓移植排斥反应。 在鼠模型系统中， 从亚致死剂量照射动物的脾脏中克隆CTL 排斥MHC不同骨髓移植物的小鼠。 结果发现 克隆的CTL事实上足以影响T细胞的排斥反应， 在致死辐射的动物中耗尽同种异体骨髓。 的 CTL对骨髓移植物的排斥反应是MHC基因特异性的 由骨髓细胞表达的产物与细胞毒性相关 个体克隆的特异性。 因为隔离的宿主CTL 可以排斥供体骨髓移植物，细胞群的能力 其可抑制宿主CTL应答以调节骨髓植入 研究了 具有特定类型抑制活性的细胞， 称为否决细胞，它可能调节宿主的排斥反应和 也介导自身耐受性，据报道存在于 骨髓，和IL-2的能力，以提高否决的活动， T细胞耗竭后骨髓中残留的抑制细胞群 这些细胞确实增强了MHC-1的植入， 不匹配的T细胞耗尽的骨髓。 人们发现，否决权 细胞通过克隆性删除前体CTL发挥作用， 这种克隆消除涉及前体的积极参与 CTL. 具体地说，否决细胞的触发被发现是介导的， 通过靶细胞激活释放穿孔素， 足以触发否决细胞 这些发现表明， 穿孔素在维持自身耐受性中的作用。 换句 研究，供体Th 2细胞因子型细胞的体内调节作用 进行了评价。 这些细胞被发现调节移植 体内反应，对细胞因子谱和细胞 人群，以及相应的保护免受移植物抗宿主病。 定义了抗原体外增殖的条件， 特异性的、由奎宁定义的Th细胞，发现它们与 调节体内移植反应。

A number of observations have suggested that host lymphocytes, specifically cytotoxic T cells (CTL) play a significant role in mediating allogenic 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 in fact 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 & correlated with the cytotoxic specificity of the individual clones. Because host CTL in isolation could reject donor marrow grafts, the ability of cell populations which could suppress host CTL responses to regulate marrow engraftment was studied. Cells with a specific type of suppressor activity, termed veto cells, which might regulate host rejection responses & also mediate self tolerance, have been reported to be present in marrow, and an ability of IL-2 to enhance the activity of veto suppressor cell populations remaining in marrow after T cell depletion had been previously found. Such cells did enhance engraftment of MHC- mismatched, T cell depleted marrow in vivo. It was found that veto cells exerted their effect by clonal deletion of precursor CTL, & that such clonal elimination involved an active participation by precursor CTL. Specifically, triggering of veto cells was found to be mediated by target cell activation with release of perforin which was sufficient to trigger veto cells. These findings indicate a possible role for perforin in the maintenance of self tolerance. In other studies, the in vivo regulatory role of donor Th2 cytokine type cells was evaluated. Such cells were found to modulate transplantation responses in vivo with effects on cytokine profiles and cell populations, &corresponding protection from graft versus host disease. Conditions were defined for the in vitro propagation of antigen, specific, cytokine-defined Th cells which were found to be similarly regulate transplantation responses in vivo.