A Leishmania homologue of receptors for activated C-kinase (LACK) induces both interferon-gamma and interleukin-10 in natural killer cells of healthyblood donors

Natural kilter (NK) cells from individuals unexposed to Leishmania organism s proliferate with high interferon (IFN)-gamma secretion in response to cru de Leishmania antigen preparations. In an attempt to identify the molecules that induce blood cells to proliferate and to secrete cytokines, we tested the effect of a 36-kDa Leishmania homologue of receptors for activated C-k inase (LACK) on peripheral blood mononuclear cells from unexposed individua ls. Mainly CD8(+) and NK cells proliferated in response to LACK, At both th e mRNA and soluble protein level, the main sources for LACK-induced IFN-gam ma and interleukin (IL)-10 were T and NK cells. Furthermore, in the presenc e of anti-major histocompatibility complex (MHC) class II antibody, there w as inhibition of LACK responses in both CD4(+) and CD16/56(+) cells, with a marked decrease in IFN-gamma but with an increase in IL-10 production. We conclude that the response to LACK is part of the response to Leishmania or ganisms in unexposed donors described elsewhere. That this NK-dominated res ponse is MC class II sensitive, whether through a direct or indirect effect , is discussed.