Leishmaniasis is a spectral disease in both animals and humans. Helper T cells (L3T4+) mediate both protective immunity and the immunosuppression accompanying progressive disease in murine infection. The recent classification of helper T cell clones into two subsets based on the secretion of interferon-gamma or BSF- 1/IL-4 suggests that the outcome of Leishmania infection may reflect the expansion of one or the other of these subsets in vivo. Preliminary data supports this hypothesis based on analysis of these cytokines by Northern analysis following extraction of mRNA from infected mice and assays for protein in vitro. This proposal seeks to: 1. clone these discrete Leishmania-specific L3T4+ T cells from groups of healing or progressing mice infected with L. major and L. donovani; 2. assess the effector functions of these cloned T cells utilizing cell transfers into infected mice; 3. identify the same phenotypically and functionally defined CD4+ T cells in the blood or bone marrow of patients with acute kala-azar or who have been cured of disease; 4. clone the human CD4+ Leishmania-specific cells. The long term goal will be to use these discrete populations of cloned T cells to screen Leishmania antigens that could function as candidate vaccines or that mediate the immunosuppression of progressive disease.
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