Effect of lymphocytes on the production of granulomonopoietic enhancing factor by fully mature macrophages.

Abstract

The granulomonopoietic enhancing factor (GM-EF) is a novel myelopoietic regulator produced by human monocyte-derived lipid-containing macrophages (MDLMs). In the present study, we examined the effect of lymphocytes on GM-EF production by preincubation of MDLMs with various preparations of lymphocyte subpopulations in cell-mixed and in double agar layer cultures. Our results showed that a cell concentration-dependent suppression of GM-EF production was noted in cultures with mitogen-activated T cells, and mitogen-activated/resting B cells, while those containing resting T cells had no such effect. Thus, GM-EF production in the presence of 1 x 10(5)/ml activated T cells or activated/resting B cells was greatly reduced to 5% or 20%, respectively. The lymphocyte-induced suppression was evident in both cell-mixed and double layer cultures, implying that the effector cells might exert their influences via mediators. Assay for cytokine activity revealed that a high level (648.2-685.2 pg/ml) of tumor necrosis factor-alpha (TNF-alpha) was found in MDLM cultures with resting/activated B cells, and in those with activated T cells high levels of both TNF-alpha (510.5 pg/ml) and interferon-gamma (IFN-gamma) (321.3 pg/ml) could be detected, whereas in cultures with MDLMs and/or resting T cells, these cytokines were not measurable. Treatment of MDLMs with either recombinant (r) TNF-alpha or rIFN-gamma invariably resulted in a dose-dependent decrease in GM-EF production with intense suppression at doses between 400-800 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)