MACROPHAGE ACTIVATION IN EXPERIMENTAL LEISHMANIASIS

实验性巨噬细胞活化的研究 利什曼病将试图定义巨噬细胞的作用 在遗传易感和抗性的反应中携带Ia 小鼠品系对主要利什曼原虫感染。 而 Balb/c小鼠发生内脏化的致命感染， 被用作弥漫性皮肤和 C57B1/6小鼠对人类的全身性利什曼病具有抗性， 严重的疾病和完全恢复后的发展 局部损伤。 不同免疫反应的原因 对这两种小鼠中的寄生虫的了解还不是很清楚 但可能与敏感Balb/c的倾向有关 小鼠品系经历不适当的，非保护性的扩张 感染后T淋巴细胞的数量。 这种T细胞的扩增 显然导致无法控制或产生免疫力， 寄生虫，一个理论证实的事实， 包括预防性环孢霉素在内的免疫调节策略 治疗可以保护和发展 抗L.主要用于易感小鼠模型。 作为 淋巴细胞可被活化的、带有Ia的 巨噬细胞，这可能是一个过度丰富的这些 刺激性巨噬细胞在感染过程中被激活， 非免疫抑制的感染Balb/c小鼠。 事实上，初步 数据显示，具有非常高水平的Ia的腹膜渗出物 与未感染的Balb/c小鼠相比， 感染的对照组。 希望本研究能有助于阐明激活的 巨噬细胞在小鼠对L. 主要是与疾病的关系。 具体而言是 腹膜腔的Ia携带巨噬细胞水平 C57 B1/6、Balb/c和环孢霉素处理的Balb/c小鼠将被 在感染后的不同时间进行比较。 此外，本发明还提供了一种方法， 感染的Balb/c小鼠将用抗Ia抗体进行免疫治疗 抗体，以进一步分析可能的 巨噬细胞活化在全身免疫调节中作用 疾病发展。 将对所有动物进行疾病随访 通过确定病变大小在每个时间点的进展， 引流淋巴结和脾脏的细胞数量和重量， 利什曼原虫向脾脏和淋巴结转移及水平 抗利什曼抗体和迟发型超敏反应 利什曼原虫抗原

The proposed study on macrophage activation in experimental leishmaniasis will attempt to define the role of macrophages bearing Ia in the response of genetically susceptible and resistant strains of mice toward Leishmania major infections. Whereas Balb/c mice develop visceralizing, fatal infections which have been used as experimental models both for diffuse cutaneous and systemic leishmaniasis in man, the C57B1/6 mice are resistant to severe disease and recover completely following the development of local lesions. The reasons for the different immune responses to the parasite in these two strains of mice is not well understood but may be related to the tendency of the susceptible Balb/c mouse strain to undergo an inappropriate, nonprotective expansion of T lymphocytes following infection. This expansion of T cells apparently leads to the inability to control or develop immunity to the parasite, a theory substantiated by the fact that various immunomodulatory strategies including prophylactic cyclosporine A treatment allows for protection and the development of immunity against L. major in the susceptible mouse model. As lymphocytes may be stimulated to expand by activated, Ia bearing macrophages, it may be that an over-abundance of these stimulatory macrophages become activated during infection in non-immunosuppressed, infected Balb/c mice. Indeed, preliminary data has shown a very high level of Ia-bearing peritoneal exudate cells does develop in infected Balb/c mice as compared to non- infected controls. It is hoped that this study will help to clarify the role of activated macrophages in the susceptibility or resistance of mice to L. major and their relation to the disease process. Specifically, the levels of Ia bearing macrophages of the periotoneal cavities of C57B1/6, Balb/c and cyclosporine treated Balb/c mice will be compared at different times following infection. In addition, infected Balb/c mice will be prophylactically treated with anti-Ia antibody in order to further analyze the possible immunoregulatory role of macrophage activation in systemic disease development. All animals will be followed for disease progression at each time point by determinations of lesion size, cell numbers and weights of the draining lymph node and spleen, metastasis of Leishmania to the spleen and lymph node and levels of anti-leishmanial antibodies and delayed type hypersensitivity toward a leishmanial antigen.