The effects of Con A-induced lymphokines from the T-lymphocyte subpopulations on human monocyte leishmaniacial capacity and H₂O₂ production

The effects of concanavalin A (Con A)-induced lymphokines from human peripheral blood mononuclear cells, enriched helper and suppressor lymphocyte populations and recombinant interferon-gamma (IFN-gamma) on the ability of monocytes to promote killing of intracellular Leishmania major (L. major) amastigotes and to induce the production of hydrogen peroxide (H₂O₂) was examined. All these mitogen-induced supernatants contained active IFN-gamma. There were no differences in the ability of these supernatants or IFN-gamma to promote the monocyte killing of the L. major amastigotes or H₂O₂ production. An increase in H₂O₂ production by monocyte monolayers was observed following the addition of either of these supernatants or IFN-gamma alone. In addition, a marked increase in the production of H₂O₂ was observed following priming with either of these mitogen-induced supernatants or IFN-gamma and the addition of a second stimulus, phorbol myristate acetate (PMA). Monoclonal antibody to IFN-gamma abrogated the increase in production of H₂O₂ by all these mitogen-induced supernatants; however, this antibody only resulted in partial inhibition of the leishmaniacidal effect of these lymphokines on human monocytes. These results would suggest that IFN-gamma is the component of the lymphokine that is largely or exclusively responsible for H₂O₂ production, while other factors in addition to IFN-gamma are ijmportant in promoting oxygen-independent mechanisms for the killing of intracellular L. major amastigotes.