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

同种异体骨髓移植中的移植物抗宿主病预防

• 批准号: 4691778
• 负责人: R E GRESS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4691778
• 关键词: T lymphocyte; bone marrow transplantation; clone cells; complement; genotype; graft versus host disease; homologous transplantation; human tissue; immunohematology; immunotherapy; monoclonal antibody; radiation immunosuppression; suppressor T lymphocyte; surface antigens; tissue mosaicism

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.

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， 已经开发了接种的骨髓、试剂和技术， 从骨髓接种物中取出这些T细胞， 这种损耗。 为此，几种鼠单克隆抗体特异性 已经开发了用于在人T细胞上表达的抗原的方法，其中三种， 有细胞毒性。 这些抗体已被利用，与 其他消耗技术，用于补体介导的T细胞裂解， 骨髓 通过现在可用的克隆形成分析，骨髓中残留的T细胞 在这种消耗之后， 细胞群 关于同种异体反应性T细胞的控制 介导移植物抗宿主病， 这种同种异体反应性已经在鼠辐射骨髓中进行 嵌合体 研究表明，这一代人受到一种独特的 T细胞基因型和T细胞成熟环境的相互作用。 的 已经证明人CTL的良好特异性足以 区分I类主要的α 1和α 2结构域变化 组织相容性使分子复杂化。 这种成熟的同种异体反应性人类 细胞毒性T细胞已经在细胞表面方面进行了进一步的研究 在与靶细胞的相互作用中利用的分子作为 旨在预防组织损伤的治疗干预 由这种同种异体反应性细胞毒性T细胞介导。