Virulent or avirulent (dhfr-ts(-)) Leishmania major elicit predominantly atype-1 cytokine response by human cells in vitro

In this study we have compared the immune response of normal human cells cu ltured in vitro to two virulent strains of Leishmania major (CC1 and LV39), and to an avirulent vaccine strain (dhfr-ts(-)) made by targeted deletion of the essential gene DHFR-TS. We utilized an in vitro system in which naiv e T cells from normal human donors were primed with autologous Leishmania-i nfected macrophages. All three parasites infected macrophages and transform ed into amastigotes within the cells. However, whereas LV39 and CC1 replica ted in macrophages, dhfr-ts(-) did not. When peripheral blood lymphocytes ( PBL) were stimulated with autologous macrophages infected with any of the t hree parasites, the lymphocytes produced a type-1-biased cytokine response. Finally, addition of IL-12 during the first stimulation period increased t he production of interferon-gamma but decreased IL-5 secretion. On the othe r hand, anti-IL-12 resulted in the opposite effect.