title: Induction of macrophage killing of Leishmania donovani by human CD4+ T cell clones.
abstract: 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-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 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-gamma 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).
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7881, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Melby
authors.forename: G
authors.initials: G
authors.lastname: Valencia-Pacheco
authors.forename: F
authors.initials: F
authors.lastname: Andrade-Narváez
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000502:physiology*; D002999:Clone Cells; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000469:parasitology; D008264:Macrophages / Q000276:immunology*; D008647:Mesocricetus
chemical_list: D000953:Antigens, Protozoan; D007371:Interferon-gamma