Gamma interferon production by combinations of human peripheral blood lymphocytes, monocytes, and cultured macrophages

Abstract

Mitogen-induced interferon (IFN) production was studied using human peripheral blood mononuclear cells and subpopulations of lymphocytes, monocytes, and cultured macrophages. Cell populations were prepared in suspension to permit quantitative analysis of the interactions among different cell types. After stimulation by staphylococcal enterotoxin A, nylon column-purified lymphocytes produced only 5% as much IFN as the peripheral blood mononuclear cells from which they were prepared. When lymphocytes were supplemented with as little as 2% monocytes, IFN production increased two- to eightfold; with the addition of up to 20% monocytes, IFN production increased further, to levels approximating those of peripheral blood mononuclear cells. Monocytes alone produced no or very little IFN. Macrophages were derived from monocytes by culturing in vitro for 7 days. The addition of 2 to 5% autologous macrophages augmented IFN production to the same extent as 2 to 5% monocytes. However, more macrophages consistently resulted in less, rather than more, IFN, so that lymphocytes with 20% monocytes produced three- to eightfold more IFN than did lymphocytes with 20% macrophages. Thus, whereas the addition of monocytes over a broad dose-response range (2 to 20%) progressively augmented IFN production, macrophages showed an optimal effect at 2 to 5%, with higher percentages being inhibitory. The IFN induced by stimulation with staphylococcal enterotoxin A was characterized as IFN-gamma by its resistance to neutralization by antibody to IFN- alpha and its inability to induce antiviral protection in embryonic bovine trachea cells.