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）是一种广泛发生在受抑制的宿主中的感染， 免疫系统 很明显，CD 4+细胞在宿主中起着核心作用。 抵御这种机会性病原体 然而，很可能， 在宿主中出现了某些细胞免疫防御机制的冗余， 特别是在T细胞的CD 8+谱系中。 由于艾滋病毒感染者 CD 4+细胞数量减少，但CD 8 + T细胞水平增加或持续 细胞，这是建议，通过刺激抗Pc和免疫调节 在CD 4+耗尽的PcP感染宿主中，CD 8+细胞的能力， PCP感染者的预后应该得到改善。 测试这些 假设，提出以下具体目标：（1）确定是否 CD 8 + 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）确定CD 8 + T细胞是否 单独或与肺泡巨噬细胞联合对Pc具有细胞毒性 （3）测定Pc免疫小鼠后提高CD_（8+）T淋巴细胞增殖能力 细胞应答和减少体内感染;和（4）测定 转移Pc诱导的CD 8 + 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.