The overall goal of this project is to define the mechanism of cell-mediated immunological unresponsiveness to Mycobacterium leprae seen in patients with lepromatous leprosy. Possible explanations for this unresponsiveness include: (1) a quantitative or qualitative defect in presentation of M. leprae specific antigens in these patients, (2) inhibition of M. leprae specific responses by antigen specific suppressor cells or alternatively by circulating anti-M. leprae antibodies, (3) a lack of M. leprae reactive T cells in the circulation, and (4) tolerance caused by binding of excess antigen to T cells. To determine the basis of specific immune unresponsiveness in lepromatous leprosy we will study the functional consequences of exposing precursors of suppressor T cells (Leu 2+, 9.3-cells) from lepromatous patients to M. leprae antigens, explore the effect of these M. leprae - treated Leu 2+, 9.3-cells on the M. leprae-induced proliferative responses of HLA-matched, M. leprae - responsive siblings of leprosy patients and analyze the functional activity and surface phenotype of T cells recovered from lepromatous skin lesions. M. leprae reactive T cell clones and T-T hybrids will be established from cells isolated from lesions or peripheral blood and extracts and culture supernatants from these clones and hybrids will be examined for the presence of soluble immunoregulatory factors. The role of defined mycobacterial antigens in the activation of each functional clone will be examined using our panel of human anti-M. leprae monoclonal antibodies, murine monoclonal antibodies, and chemically defined macromolecules derived from leprosy bacilli. The results of these studies should clarify the basis of M. leprae specific immune unresponsiveness, and thereby lead to new methods of intervention in this and possibly other infectious states associated with specific anergy (e.g. leishmaniasis).
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| Mohagheghpour, N; Gelber, R R; Engleman, E G (1987) T cell defect in lepromatous leprosy is reversible in vitro in the absence of exogenous growth factors. J Immunol 138:570-4 |
