FACTORS CONTROLLING GRAFT HOST INTERACTIONS

本项目的目的是阐明免疫遗传学，细胞， 并最终从分子上揭示了自然宿主抵抗力的机制 外来的，父母的，可能是同基因的或 自体造血干细胞和祖细胞移植物。 Amomg the 该项目的主要理由是：1）可能存在一类 免疫活性非T细胞能够介导这种抗性， 细胞表面抗原的免疫遗传特异性识别 造血组织相容性（Hh）基因，2）可能的相关性， 作为细胞相互作用调节或 维持正常的造血，和3）这种抵抗在 临床骨髓移植 计划进行一系列体内和体外研究， 体内耐药性分析的优点和新的体外模型 造血抵抗 体外模型将用于分析 接触依赖性和独立性，免疫遗传特异性， 非特异性，k刺激和抑制，细胞之间的相互作用 自然杀伤（NK）细胞样脾效应细胞和原始 骨髓来源的造血祖细胞。 体内分析 效应-靶细胞相互作用的遗传学将被应用于 选择的Hh不相容的同种异体和半同基因（F1杂种-亲本） 宿主-移植物供体组合。 体外功能分析 效应-靶骨髓细胞相互作用将集中在特异性和 对红系和髓系祖细胞的非特异性调节作用， 这些细胞相互作用与正常造血的相关性。 进一步 体外研究将表征与NK相关的效应细胞， 细胞，并将分析遗传和其他机制，调节效应 活动 检查细胞免疫遗传控制的体内研究 效应细胞和造血靶细胞之间的相互作用是 正在完成的自然阻力，涉及 H-1D/Hh-1位点。 目前正在两个领域积极进行体外研究; 鉴定定向造血祖细胞， 涉及NK样效应细胞的体外调节， 对效应细胞本身的表征。 我们也在介绍 补充体外分析的两种方法，即， 各种类型造血集落形成的体内易感性 细胞（体外检测）和体内增殖能力 干/祖细胞已经在体外暴露于确定的效应物 细胞群

The objective of this project is to elucidate the immunogenetic, cellular, and ultimately molecular, mechanisms underlying the natural host resistance to the proliferation of foreign, parental, and possibly syngeneic or autologous, grafts of hemopoietic stem and progenitor cells. Amomg the major rationales for this project are 1) possible existence of a class of immunocompetent non-T cells capable of mediating this resistance via immunogeneticaly specific recognition of cell surface antigens controlled by hemopoietic histocompatibility (Hh) genes, 2) possible relevance of the resistance as a manifestation of cellular interactions regulating or maintaining normal hemopoiesis, and 3) possible role of such resistance in clinical bone marrow transplantation. A series of in vivo and in vitro studies are planned mainly taking advantage of an analysis of in vivo resistance and a new in vitro model of hemopoietic resistance. The in vitro model will serve for analysis of contact-dependent and independent, immunogenetically specific and nonspecific,k stimulatory and suppressive, cellular interactions between natural killer (NK) cell-like splenic effector cells and primitive hemopoietic progenitor cells of bone marrow origin. Analysis in vivo of the genetics of effector-target cell interactions will be applied to selected Hh-incompatible allogeneic and semisyngeneic (F1 hybrid-parental) host-graft donor combinations. Functional analysis in vitro of effector-target bone marrow cell interactions will focus on specific and nonspecific regulatory influences on erythroid and myeloid progenitors and relevance of such cellular interactions in normal hemopoiesis. Further studies in vitro will characterize the effector cells in relation to NK cells, and will analyze genetic and other mechanisms that modulate effector activities. In vivo studies examining the immunogenetic control of the cellular interactions between the effector cells and hemopoietic target cells are being completed with respect to the natural resistance involving the H-1D/Hh-1 locus. In vitro studies are being actively pursued in two areas; the identification of committed hemopoietic progenitors that are subjected to modulation by NK-like effector cells in vitro and further characterization of the effector cells themselves. We are also introducing two approaches that supplement the in vitro analysis, namely, analysis of the susceptibility in vivo of various types of hemopoietic colony forming cells (as detected in vitro) and the proliferative capacity in vivo of stem/progenitor cells that had been exposed in vitro to defined effector cell populations.