GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS IN ALLOGENIC BONE MARROW TRANSPLANTATION

正在努力预防或控制 人异基因骨髓移植中的移植物抗宿主病。 由于这种移植物抗宿主病是由同种异体反应性T细胞介导的 接种的骨髓、试剂和技术已经发展到 将这些T细胞从骨髓接种中移除，以衡量 那种枯竭。为此，几种小鼠特异性的单抗 人类T细胞上表达的抗原已经被开发出来，其中三种 具有细胞毒性。这些抗体已经被解开，与 补体介导的T细胞裂解的其他耗竭技术 骨髓。通过目前可用的克隆形成试验，骨髓中残留的T细胞 在这样的消耗之后，其水平不到总的0.01% 细胞数量。关于同种异体反应性T细胞的控制 介导移植物抗宿主病，对移植物抗宿主病来源或代的研究 这种同种异体反应已经在小鼠辐射骨髓中进行过。 嵌合体。已经表明，这一代人受到一种独特的 T细胞基因分型与T细胞成熟环境的相互作用这个 人类CTL的良好特异性已被证明足以 区分I类专业的α1和α2结构域变化 组织相容性使分子复杂化。如此成熟的同种异体反应的人类 细胞毒性T细胞在细胞表面得到了进一步的研究 在与靶细胞相互作用中用作基础的分子 旨在预防组织损伤的治疗性干预 由这种同种异体反应性细胞毒性T细胞介导。

Efforts are being directed towards the prevention or control of graft-versus-host disease in human allogeneic bone marrow transplantation. Since such graft-versus-host disease is mediated by alloreactive T cells in the inoculated marrow, reagents and techniques have been developed to remove these T cells from the marrow inoculum and to measure the success of that depletion. To this end, several murine monoclonal antibodies specific for antigens expressed on human T cells have been developed, three of which are cytotoxic. These antibodies have been untilized, in conjunction with other depletion techniques, for complement-mediated lysis of T cells in marrow. By a clonogenic assay now available, residual T cells in marrow following such a depletion are at a level of less than 0.01% of the total cell population. With respect to the control of alloreactive T cells mediating graft-versus-host disease, studies on the orgin or generation of such alloreactivity have been undertaken in murine radiation bone marrow chimeras. It has been shown that the generation is influenced by a unique interaction of T cell genotype and the T cell maturation environment. The fine specificity of human CTL has been demonstrated to be sufficient to distinguish among alpha 1 and alpha 2 domain changes of class I major histocompatibility comples molecules. Such mature alloreactive human cytotoxic T cells have been further studies with respect to cell surface molecules utilized in their interactions with target cells as the basis for therapeutic interventions with the intent of preventing tissue damage mediated by such alloreactive cytotoxic T cells.