Receptor-specific modulation of myelopoiesis by recombinant DNA-derived interleukin 2

T cells and T cell-derived lymphokines have been implicated in the regulation of myelopoiesis. This study examines the regulatory effects of recombinant DNA-derived human IL 2 on the phagocyte progenitor cell (CFU-GM), utilizing a receptor-specific model for T cell regulation of myelopoiesis. IL 2 receptors were induced on immunopurified marrow T cells by triggering the T cell antigen receptor complex with CD3 monoclonal antibody. IL 2 receptor expression was assessed by cytofluorography with IL 2 receptor monoclonal antibody. IL 2 receptor-positive and IL 2 receptor-negative marrow T cells were cocultured with autologous adherent and T cell-depleted marrow mononuclear cells in the absence and presence of various concentrations of IL 2. In the presence of IL 2 receptor-positive T cells, IL 2 caused a dose-dependent inhibition of CFU-GM (86% at 10(2) U/ml). IL 2 did not inhibit CFU-GM in the absence of T cells or in the presence of IL 2 receptor-negative T cells. The addition of IL 2 receptor blocking monoclonal antibody completely abrogated IL 2-induced inhibition of CFU-GM. Conditioned media prepared from IL 2 receptor-positive marrow T cells in the presence of IL 2 also inhibited CFU-GM expression from marrow NAB-T cells (50% +/- 16). In contrast, conditioned media from IL 2 receptor-positive T cells prepared in the absence of IL 2 or from IL 2 receptor-negative T cells prepared in the presence or absence of IL 2 did not significantly affect CFU-GM growth. IL 2 receptor-positive, but not IL 2 receptor-negative, T cells released large amounts (190 +/- 60 U/10(6) cells X ml-1) of IFN-gamma but only low amounts of tumor necrosis factor beta (less than 10 U/ml) in response to IL 2. In control experiments, recombinant DNA-derived IFN-gamma caused a 37% +/- 19 inhibition of CFU-GM in the presence of resting T cells and adherent cells. However, IFN-gamma failed to inhibit CFU-GM in the presence of activated (IL 2 receptor-positive) T cells, indicating that release of IFN-gamma cannot solely explain IL 2-induced inhibition of CFU-GM. The addition of neutralizing IFN-gamma monoclonal antibody partially abrogated IL 2-induced inhibition of CFU-GM (41 to 60%) in the presence of CD3-triggered T cells, suggesting that although IFN-gamma participates in IL 2-induced inhibition of myelopoiesis, it is not the sole mediator of that inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)