INDUCTION OF MACROPHAGE KILLING OF LEISHMANIA-DONOVANI BY HUMAN CD4-CELL CLONES( T)

Immunity in leishmaniasis is mediated by T cells, but protective respo nses in humans have not been fully defined. In this study, the functio nal activity of CD4+ T cell clones derived from an immune individual w as investigated to identify potentially protective responses. The T ce lls proliferated and produced interferon-gamma (IFN-gamma) 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 infecte d monocytes isolated from an HLA-DR,DQ matched donor. All of the clone s which demonstrated antigen specific reactivity by proliferation or c ytokine 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 leve l of amastigote-induced IFN-gamma secretion and anti-leishmanial activ ity. This approach enables the identification of potentially protectiv e immune responses in humans at the clonal level, and offers a means f or the identification of the relevant antigen(s).