INDICATIONS OF THE PROTECTIVE ROLE OF NATURAL-KILLER-CELLS IN HUMAN CUTANEOUS LEISHMANIASIS IN AN AREA OF ENDEMICITY

The role of natural versus acquired immunity to Leishmania aethiopica infection in humans is the focus of our studies, We found in previous studies that mononuclear cells from nonexposed healthy Swedish donors responded to Leishmania antigen stimulation by proliferation and gamma interferon production. The main cell type responding was CD3(-) CD16/ 56(+) natural killer (NK) cells. These findings led us to suggest that the potential to produce a rapid, nonacquired NK cell response may be a protective phenotype, In order to test this hypothesis, an area in Ethiopia where Leishmania is endemic was selected, and peripheral bloo d mononuclear cells were obtained from individuals who had lived in th e area most of their lives but had no evidence of past or present leis hmaniasis, Their responses were compared with those of confirmed leish maniasis patients from the same region with active lesions or cured le ishmaniasis lesions, Cells from these donors were stimulated in vitro with L. aethiopica antigen. Responses were measured by proliferation, cytokine production, and phenotype analysis by fluorescence-activated cell sorting. The association of NRAMP1 alleles with the studied pheno type and susceptibility to L. aethiopica-induced leishmaniasis was als o evaluated, The results show that Leishmania antigens can induce NK c ell and CD8(+)-T-cell responses in vitro. This is clearly seen in prol iferating cells from the cured (immune) individuals and the apparently protected controls from the area of endemicity, It contrasted with th e reactivity of the patients, where some NR proliferation was coupled with enhanced CD4(+)-T-cell proliferation. We conclude from these obse rvations that NK cells and CD8(+) cells proliferating in response to L eishmania stimulation are involved in protection from and healing of ( Ethiopian) cutaneous leishmaniasis; however, such mechanisms appear to be unrelated to the NRAMP1 host resistance gene.