title: The effect of interleukin 2 on Fc-gamma receptor function of human monocytes requires specific intercellular interaction.
abstract: We examined the effect of interleukin 2 (IL 2) on the capacity of human monocytes to secrete reactive oxygen species triggered via Fc-gamma receptor (Fc gamma R) function as measured by chemiluminescence (CL). IL 2 did not activate highly purified (hp) monocytes to respond to Fc gamma R-mediated phagocytic stimulation with an enhanced respiratory burst activity, unless low numbers of T lymphocytes had been cocultured with hp monocytes. The degree of monocyte activation in peripheral blood mononuclear cells (PBMC) by IL2 was dependent on T lymphocytes to monocytes ratios as well as on IL 2 concentrations. Optimal Fc gamma R function was detected with IL 2 concentrations of 60 to 600 U/ml and one to two T lymphocytes per monocyte, whereas higher cellular ratios were suppressive. Supernatants from IL 2-treated PBMC contained interferon-gamma (IFN-gamma) and monocyte activating factor (MAF) activity (= enhanced monocytic Fc gamma R mediated CL). The secretion of both cytokine activities was strongly enhanced by a cooperative function of monocytes. The correlation of IL 2-induced secretion of IFN-gamma and MAF activity was striking; however, monoclonal anti-IFN-gamma antibodies failed to abrogate IL 2-stimulated and lymphocyte-dependent monocyte activation. Although IL 2 had no direct monocyte activating effect, pretreatment of hp monocytes with IL 2 led to a monocyte priming: subsequent coculture with autologous control T lymphocytes enhanced the monocyte Fc gamma R-mediated CL response. The priming of monocytes by IL 2 was dependent on the interaction of IL 2 with the monocytic IL 2 receptor, as shown by inhibition experiments with anti-IL 2 receptor monoclonal antibodies. Thus, we observed an IL 2-driven monocyte/T lymphocyte interaction leading to an increased Fc gamma R-mediated monocytic respiratory burst activity and to the secretion of a soluble MAF activity, but there were no detectable amounts of IFN-gamma.
authors.affiliation: Department of Immunology and Cell Biology, Forschungsinstitut Borstel, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ennen
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: H D
authors.initials: HD
authors.lastname: Flad
mesh_terms: D000943:Antigens, Differentiation / Q000276:immunology*; D001770:Blood Bactericidal Activity; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D007376:Interleukin-2; D011961:Receptors, Fc; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D013481:Superoxides; D007371:Interferon-gamma