INDUCTION OF IMMUNITY AND TOLERANCE TO M LEPRAE

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This research has two main objectives: (1) To evaluate the immune response of normal Lewis rats following intrasdermal immunization with heat-killed M. leprae and a combination of heat-killed M. leprae plus viable BCG, using in vitro techniques for assessment of cell-mediated immunity (CMI). Characterization of the immune response that develops following intradermal administration of the above vaccines into normal Lewis rats will be based on: (a) the kinetics (onset and duration) of the developing immune response, (b) the antigen threshold required for its induction, and (c) the efficiency (rate and level of deveopment) and duration of immunological recall following secondary immunization with heat-killed M. leprae antigens and viable VCG. The in vitro parameters to be used for assessment of CMI expreession following co-culture of in vivo antigen-primed spleen and lymph node cells with M. leprae and PPD will be: (a) specific-antigen-induced lymphocyte proliferation, (b) release of migration inhibition factor, and (c) production of interleukin-2. The level of CMI, as measured by in vitro analysis, will be compared with the level of in vivo resistance by challenge with viable M. leprae. (2) To investigate the immunological mechanism(s) responsible for M. leprae-induced tolerance in the Lewis rat using in vitro methods for assessment of antigen-specific lymphocyte activation. The role of macrophages, lymphocytes, and serum factors will be examined both in vitro and in vivo. Spleen and lymph node cells from Lewis rats tolerant to M. leprae antigens will be examined for their ability to produce various lymphokines (interleukin-2, migration inhibition factor, macrophage activating factor, and interferon) and a cytokline (interleukin-1) following co-culture wit M. leprae antigens, PPD and Con A. Finally, experiments will be conducted to determine if M. leprae-induced tolerance results in decreased resistance using in vivo challenge with viable M. leprae. Results from this study may prove useful for designing future clinical trials with antileprosy vaccines and may provide valuable information concerning the immunological mechanisms responsible for the CMI dysfunction characteristic of lepromatous leprosy in humans. Our long-term goal is to develop a combined immuno- and chemotherapeutic treatment of leprosy that could be applied clinically.