MECHANISMS OF CD8+ T CELL DEFENSE AGAINST PNEUMOCYSTIS

描述：(改编自申请人摘要)。卡氏肺孢子虫 肺炎(PCP)是一种在宿主中广泛发生的感染。 免疫系统。很明显，CD4+细胞在宿主中起着中心作用 对这种机会主义病原体的防御。然而，很可能是 细胞免疫防御的某些机制在宿主中存在冗余， 尤其是T细胞的CD8+谱系。由于艾滋病病毒感染者 降低了CD4+细胞数量，但增加或维持了CD8+T细胞水平 细胞，有人认为通过刺激抗Pc和免疫调节 CD8+细胞在CD4+耗竭的PCP感染宿主中的能力 PCP感染者的结局应该有所改善。为了测试这些 假设，提出了以下具体目标：(1)确定是否 CD8+T细胞的细胞因子产物激活肺泡巨噬细胞 体外吞噬和杀伤Pc；(2)测定CD8+T细胞 对Pc单独或与肺泡巨噬细胞相关的细胞毒作用 体外培养；(3)Pc免疫提高CD8+T细胞的能力 细胞反应和减少体内感染；以及(4)确定能力 转移Pc诱导的CD8+T细胞以调节体内感染。

DESCRIPTION: (Adapted from Applicant's Abstract). Pneumocystis carinii pneumonia (PcP) is an infection that occurs widely in hosts with suppressed immune systems. It is clear that CD4+ cells play a central role in host defense against this opportunistic pathogen. However, it is likely that redundancy in some mechanisms of cellular immune defense occurs in the host, specifically in the CD8+ lineage of T-cells. Since HIV-infected individuals have reduced CD4+ cell numbers, but increased or sustained levels of CD8+ T cells, it is proposed that by stimulating the anti-Pc and immunomodulatory capacities of the CD8+ cells in CD4+-depleted PcP-infected hosts, the outcome of PcP-infected individuals should improve. To test these hypotheses, the following specific aims are proposed: (1) determine whether cytokine products of CD8+ T cells activate alveolar macrophages for phagocytosis and killing of Pc in vitro; (2) determine whether CD8+ T cells are cytotoxic towards Pc alone or in association with alveolar macrophages in vitro; (3) determine ability of immunization with Pc to increase CD8+ T cell responses and decrease infection in vivo; and (4) determine the ability of transfer of Pc-elicited CD8+ T cells to modulate infection in vivo.