Production of granulocyte-macrophage colony stimulating factor by large granular lymphocytes: role in activation of human neutrophil function

Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay. Furthermore, Mycobacterium avium-M. intracellulare was found to induce the production of this hemopoietic growth factor. Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria. GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes. The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers. Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation. Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation. From these studies, LGL and monocytes are capable of responding to M. avium-M. intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes. Infection with Mycobacterium avium-M. intracellulare is one of the most common mycobacterium-related diseases in patients with AIDS (7, 15, 28). M. avium-M. intracellulare i