Leishmania: Naive human T cells sensitized with promastigote antigen and IL-12 develop into potent Th1 and CD8(+) cytotoxic effectors

The differentiation of naive human T cells into Leishmania-specific Th1 or cytotoxic effector cells was examined by sensitizing T cells in vitro with dead Leishmania antigen in the presence or absence of IFN-gamma or IL-12. T hese Leishmania-specific T cell lines proliferated and produced cytokines i n response to challenge with autologous Leishmania-infected macrophages. Se nsitization in the presence of IL-12 or IFN-gamma induced Leishmania-specif ic human Th1 responses, with IL-12 inducing more potent Th1 responses. Howe ver, IL-12-induced Th1 responses were IFN-gamma dependent. T cell lines exh ibited Th2 or Th0 phenotypes when primed in the absence of cytokines. Only T cell lines primed in the presence of IL-12 contained high percentages of CD8(+) cells. These cells lysed autologous Leishmania-infected but not unin fected macrophages in an MHC-dependent manner. Thus, this in vitro sensitiz ation system can be used to delineate the conditions for optimally priming human Leishmania-specific effector cells. (C) 1999 Academic Press.