REGULATION OF ERYTHROPOIESIS

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.