Natural killer cells in cross-regulation of IL-12 by IL-10 in Leishmania antigen-stimulated blood donor cells

We have previously shown that natural killer (MK) cells play a role in prot ection against leishmaniasis. Furthermore, we have shown that NK cells in m ononuclear cells derived from unexposed donors are induced to proliferate i n vitro in response to leishmanial antigens. Since interleukin (IL)-12, a s trong inducer of NK cells, acts on the early events in NK cells and T-cells , and is considered as an adjuvant for use in a potential antileishmaniasis antigen, we wished to investigate how this cytokine influences the in vitr o Leishmania induced proliferative and cytokine response in healthy donors. We demonstrate that in an innate response to Leishmania antigen involving NK cells, a critical level of IL-12 is required to induce interferon (IFN)- gamma secretion below which, IL-10 is released in amounts which apparently inhibit IFN-gamma secretion and cellular proliferation. However, at higher IL-12 levels, there is simultaneous secretion of IFN-gamma and IL-10 as wel l as proliferation of cells. In a similar vein, exogenous IL-10 in turn inh ibited IFN-gamma secretion as well as proliferation when used at low/medium concentrations, but at high concentrations this effect was abolished and r eplaced by the simultaneous detection of IFN-gamma, IL-10 and proliferation . The contribution of NI( cells in cross regulation of these two very impor tant immuneregulatory cytokines and the effect of exogenous IL-12 in a Leis hmania driven response are discussed.