INDUCTION OF IMMUNITY AND TOLERANCE TO M LEPRAE

这项研究有两个主要目标： (1)评价正常刘易斯大鼠在以下情况下的免疫应答 用热灭活的M.麻风病和 热灭活M.麻风加活卡介苗，使用体外技术， 细胞介导免疫（CMI）。 免疫的表征 皮内给予上述药物后产生的反应 将疫苗注射到正常刘易斯大鼠中的方法将基于：（a）动力学（发作 和持续时间），（B）抗原阈值 （c）效率（培训的速度和水平） 发展）和免疫回忆的持续时间 热灭活M.麻风抗原和活性VCG。 的in 用于评估以下CMI表达的体外参数 体内抗原致敏的脾和淋巴结细胞与M. 麻风和PPD将是：（a）特异性抗原诱导淋巴细胞 增殖，（B）迁移抑制因子的释放，和（c） 白细胞介素-2的产生。 CMI水平，如通过体外 分析，将与体内抗性水平进行比较， 挑战可行的M。麻风病人 (2)目的探讨M. 麻风诱导的耐受性在刘易斯大鼠使用体外方法， 抗原特异性淋巴细胞活化的评估。 的作用 巨噬细胞、淋巴细胞和血清因子将在体外进行检查， 和体内。 从刘易斯M. 将检查麻风抗原产生各种 淋巴因子（白细胞介素-2，移动抑制因子，巨噬细胞 激活因子和干扰素）和白细胞介素-1（IL-1） 与M.麻风抗原PPD和Con A 最后， 将进行实验以确定M.麻风诱导耐受 使用活M. 麻风病人 这项研究的结果可能有助于设计未来的临床 抗麻风疫苗的临床试验，可能提供有价值的信息 关于负责CMI功能障碍的免疫机制， 具有瘤型麻风病的特征。 我们的长期目标是 开发一种麻风病的免疫和化疗联合治疗方法， 可以应用于临床。

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.