Promotion of hematopoietic stem cell differentiation in vitro by a soluble mediator, allogeneic effect factor

This study was designed to investigate the effects of allogenic effect factor (AEF), a soluble mediator derived from short-term mixed lymphocyte cultures (MLC) of in vitro alloantigen-primed T cells, on cultures of murine bone marrow cells. Cultures established under suboptimal conditions namely, in the absence of a pre-established adherent cell layer as required in conventional Dexter-type cultures--declined and lost their stem cell activity rapidly. In contrast, supplementation of these cultures, at initiation and thereafter, with AEF, but not with T cell growth factor (TCGF), induced cell growth and proliferation for several weeks. Such AEF-supplemented cultures exhibited cellular heterogeneity and stem cell activity for significantly longer periods than the control cultures. Even in conventional Dexter cultures, established under optimal conditions, AEF had a beneficial effect on cellular growth and proliferation and myeloid progenitor cell (CFU-C) activity. Furthermore, cell capable of synergizing with suboptimal numbers of mature T cells in con A-induced mitogenic responses, shown by others to be pre-T cells, were detected in the AEF-supplemented cultures for several weeks.