Leprosy is a spectral disease which provides a unique clinical model for investigating resistance and tolerance to an infectious pathogen. It is within the tissue lesions that the battle between the immune and the pathogen is joined. Therefore, our approach has been aimed at studying immune cells in lesions which are likely to be critical to the pathogenesis of leprosy. Hence, this study is designed to investigate the immunoregulatory processes that occur in lesions of leprosy. Our demonstrated expertise with monoclonal antibodies and immunoperoxidase staining will be used to characterize cells in situ in lesions by studying their cell surface phenotype and microanatomical location. These studies will be advanced by the detection of mRNA coding for proteins critical to immunoregulation by in situ hybridization. We have developed new methods of studying the immune function of cells in lesions by extracting and purifying cells from skin biopsy specimens of leprosy patients. Limiting dilution analysis will be performed on lymphocytes to provide information as to the relative frequency of M. leprae reactive cells from lesions versus blood and the delineation of immunodominant M. leprae antigens. In addition, cloning of T-helper and T-suppressor lymphocytes from tissue-derived cells will provide reagents for determination of 1) the range of antigens and epitopes recognized by the immunologic repertoire of patients; 2) the functional response elicited by a given epitope; and 3) the mechanism by which T- suppressor cells contribute to immunologic tolerance. The cumulative effect of the attainment of these goals will be the understanding of the immunoregulatory processes that contribute to resistance and tolerance to M. leprae and the identification of the precise epitopes that contribute to protective immunity. This will lead to more exacting immunodiagnostic reagents and more logical intervention strategies.
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