Induction of macrophage killing of Leishmania donovani by human CD4+ T cell clones

Immunity in leishmaniasis is mediated by T cells, but protective responses in humans have not been fully defined. In this study, the functional activity of CD4+ T cell clones derived from an immune individual was investigated to identify potentially protective responses. The T cells proliferated and produced interferon-gamma (IFN-γ) in response to a soluble Leishmania donovani antigen extract and live amastigotes. There was considerable variation in the anti-leishmanial activity of the T cell clones when they were co-cultured with L. donovani infected monocytes isolated from an HLA-DR,DQ matched donor. All of the clones which demonstrated antigen specific reactivity by proliferation or cytokine production induced some degree of inhibition of intracellular parasite replication, but only a few of the clones induced pronounced leishmanicidal activity. There was strong correlation between the level of amastigote-induced IFN-γ secretion and anti-leishmanial activity. This approach enables the identification of potentially protective immune responses in humans at the clonal level, and offers a means for the identification of the relevant antigen(s).