Stimulation of human BFU(E) by products of human monocytes and lymphocytes

Regulation of normal human peripheral blood BFU(E) by lymphocytes and monocytes was investigated using plasma clot cultures. Monocyte depletion from peripheral blood mononuclear cells (MNC) resulted in 28 to 98% inhibition of BFU(E) growth in 16 of 17 experiments, but T lymphocyte depletion caused no decrease in BFU(E). When both T cells and monocytes were removed there was an 80% decrease in BFU(E) growth. Addition of as few as 10(4) monocytes alone increased BFU(E) to 88% of expected levels, but addition of 5 x 10(4) T lymphocytes resulted in an increase to only 57% of anticipated BFU(E) numbers. Conditioned media (CM) from 5 x 10(5) to 10(6) unstimulated T lymphocytes per ml stimulated BFU(E) growth from cultures of non-adherent cells, but not from cultures of T cell depleted MNC. Monocyte CM produced peak (2.2-fold) stimulation with only 10(5) monocytes/ml. CM from 5 x 10(5) to 10(6) monocytes/ml had no detectable erythroid burst promoting activity (BPA). Thus, unstimulated monocytes produce BPA, and at high cell concentrations, also produce a presumed inhibitor of BPA production or biologic activity. Although T cells may play some role in control of BFU(E), monocytes appear to be critical for optimal BFU(E) growth in vitro.