REGULATION OF ERYTHROPOIESIS

本研究的主要目的是探讨细胞调控 特别是正常和过度抑制人类 体外红细胞生成。 一般造血调节（即 骨髓生成和血小板生成）将在一般检查后进行评估。 通过红系祖细胞的体外研究阐明了这些原理。 本研究的具体目的是：1）探索Ia（DR）的作用 和“DR样”）抗原在红系祖细胞调节中的作用，2）检查 红系抑制细胞的性质及其与祖细胞的相互作用 为了确定造血抑制的程度， 遗传限制，3）表征红系抑制细胞， 其抑制机制; 4）丰富外周血 单核细胞的抑制细胞的最终目标是提供 为了研究抑制子-祖细胞， 交互. 抑制细胞与造血细胞减少相关 也将在这方面加以利用，5）最后利用 通过这些研究获得的信息，以检查红细胞的病因 先天性发育不全性再生障碍性贫血及其他 再生障碍状态 这项研究在很大程度上依赖于体外克隆测定 对于多能和单能定向造血祖细胞。 物理方法如免疫玫瑰花结、抗体和补体介导 裂解、荧光激活细胞分选仪（FACS）技术和氚标记的 胸苷“自杀”将用于选择造血祖细胞， 表面抗原表达和特异性细胞周期抑制细胞 动力学，以实现上述目的。 知识 从这些研究中获得的信息将有助于提高对正常 和异常造血 对红系细胞的认识 表面，红系抑制细胞的作用机制，以及 红细胞再生障碍性贫血的病理生理学知识无疑会导致 治疗再生障碍性疾病的改进策略， 或后天获得。

The major objective of this research is to explore the cellular regulation and in particular the normal and excessive suppression of human erythropoiesis in vitro. Regulation of hematopoiesis in general (i.e. myelopoiesis and thrombopoiesis) will be evaluated later after general principles are elucidated by the in vitro study of erythroid progenitors. The specific aims of this study are to 1) explore the role of the Ia (DR and "DR like") antigens in erythroid progenitor regulation, 2) examine the nature of erythroid suppressor cells and their progenitor interactions in order to determine the extent to which hematopoietic suppression is genetically restricted, 3) characterize the erythroid suppressor cell and the mechanism of its suppression, and 4) enrich peripheral blood mononuclear cells for suppressor cells with the ultimate goal of providing "pure" populations of cells in order to study suppressor-progenitor interactions. Suppressor cells associated with hematopoietic cytopenias will also be utilized in this regard, and 5) finally utilize the information gained by these studies to examine the etiology of the red cell aplasia of congenital hypoplastic (Diamond-Blackfan) anemia and other aplastic states. The research relies heavily upon in vitro clonal assays for multipotent and unipotent committed hematopoietic progenitors. Physical methods such as immune rosetting, antibody and complement mediated lysis, fluorescence activated cell sorter (FACS) techniques and tritiated thymidine "suicide" will be used to select hematopoietic progenitors and suppressor cells for surface antigen expression and specific cell cycle kinetics in order to achieve the aims described above. The knowledge gained from these studies will lead to an improved understanding of normal and abnormal hematopoiesis. The understanding of the erythroid cell surface, the mechanism of action of erythroid suppressor cells, and knowledge of the pathophysiology of red cell aplasia will no doubt lead to improved strategies for the treatment of aplastic states, either congenital or acquired.