FACTORS CONTROLLING GRAFT HOST INTERACTIONS

这项研究项目的长期目标是阐明 免疫遗传、细胞机制，最终是分子机制 自然寄主对外源、亲本和 可能是同基因或自体的造血干细胞和祖细胞移植物 细胞。这个项目的主要理由有1)可能 一类免疫活性非T细胞的存在 这种耐药性是通过免疫遗传学对细胞表面的特异性识别而产生的 由造血组织相容性基因控制的抗原，2) 耐药性可能与细胞性疾病的表现有关 调节或维持正常造血的相互作用，以及3)可能 这种耐药性在临床骨髓移植中的作用。 在本提案中，一系列体内和体外研究是 计划好的，主要是利用新开发的竞争性 体内耐药抑制分析及一种新的体外模型 造血抵抗力。体外模型，尽管它的性质仍然是 不完全理解，将用于分析接触依赖和 独立的、免疫遗传特异性的和非特异性的、刺激性和 自然杀伤(NK)细胞样细胞之间的抑制性细胞相互作用 脾效应细胞与原始骨造血祖细胞 起源于骨髓。效应-靶细胞遗传学的活体分析 交互作用将应用于选定的HH不相容的同种异体和 半同基因(F1杂交亲本)宿主-移植物供体组合。 效应靶向骨髓细胞的体外功能分析 互动将集中在特定和非特定的监管影响上 红系和髓系祖细胞及其相关性的研究 正常造血中的相互作用。进一步的体外研究将 确定效应细胞与NK细胞的关系，并将分析 调节效应器活动的遗传和其他机制。

It is the long-term objective of this research project 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. Among the major rationales for this project are 1) possible existence of a class of immunocompetent non T cells capable of mediating this resistance via immunogenetically 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. In the present proposal, a series of in vivo and in vitro studies are planned, mainly taking advantage of a newly developed competitive inhibition analysis of in vivo resistance and a new in vitro model of hemopoietic resistance. The in vitro model, though its properties are stil imcompletely understood, will serve for analysis of contact-dependent and independent, immunogenetically specific and nonspecific, 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.