Susceptibility of lymphokine-resistant Leishmania to cell contact-mediated macrophage activation

Lymphokine-mediated activation of macrophages is considered an important host defense mechanism against Leishmania. Recently we identified an additional mechanism of T cell-mediated macrophage activation of defense against Leishmania that is apparently lymphokine-independent and cell contact-dependent but not cytotoxic to host cells. In the present study we determined that strains of Leishmania mexicana that are not susceptible to the antimicrobial effects that result from lymphokine activation are nonetheless susceptible to antileishmanial effects resulting from T cell contact-mediated macrophage activation. Lymphocytes capable of activating macrophages by the cell contact-dependent mechanism appeared transiently in C57BL/6 mice infected with one of these L. mexicana strains. Our findings provide further evidence for fundamental distinctions between lymphokine- and contact-mediated antileishmanial defense. The results suggest that in addition to resistance to lymphokine-mediated effects, suppression of cell contact-mediated defense may account for chronicity in these infections.