Monoclonal antibody assessments of T cell interactions in erythropoietin studies

The contemporary application of clonal assay techniques has greatly expanded our knowledge of the regulation of hematopoiesis. Our efforts have been directed toward the investigation of non-erythropoietin-mediated regulation of human erythropoiesis in the form of cell-to-cell interaction between mature T cells and erythroid progenitors. Our data indicate that three such progenitors, the early marrow erythrocyte precursor BFU-E, the more mature marrow erythrocyte precursor, CFU-E and the peripheral blood BFU-E, each exhibit totally different requirements for their colony expression in culture, with respect to the absence of erythropoietin and the presence of mature T cells or their products. The capacity of erythroid progenitors to withstand incubation in the absence of erythropoietin appears to be a characteristic of immature rather than mature erythroid progenitors. Furthermore, use of OKT3 antibody depletion techniques shows that peripheral blood-derived BFU-E appear to depend upon mature lymphocytes or T cell-conditioned medium for erythropoietin-stimulated differentiation while bone marrow BFU-E and CFU-E have no requirement for mature T cells to produce erythropoietin-dependent maturation. Our results, plus a vast array of data provided by other investigators in the field, are integrated into a proposed framework for further investigation of T cell induction of erythropoietin-dependent erythroid differentiation aimed at more specifically identifying the inducer cell subset(s) in that system.