MECHANISMS OF CD8+ T CELL DEFENSE AGAINST PNEUMOCYSTIS

CD8 T 细胞防御肺囊虫的机制

• 批准号: 6183783
• 负责人: JAMES M BECK
• 金额: $ 26.43万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183783
• 关键词: Pneumocystis carinii; alveolar macrophages; cellular immunity; cytokine; cytotoxic T lymphocyte; laboratory mouse; leukocyte activation /transformation; microorganism immunology; natural killer cells; tissue /cell culture

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.

描述：（改编自申请人的摘要）。 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，CD4+细胞在宿主细胞中发挥着核心作用。 防御这种机会性病原体。 然而，很可能 宿主体内某些细胞免疫防御机制出现冗余， 特别是在 T 细胞的 CD8+ 谱系中。 由于艾滋病毒感染者 CD4+ 细胞数量减少，但 CD8+ T 水平增加或持续 细胞，建议通过刺激抗PC和免疫调节 CD4+ 耗尽的 PcP 感染宿主中 CD8+ 细胞的能力， 五氯苯酚感染者的预后应该会有所改善。 为了测试这些 假设，提出以下具体目标：（1）确定是否 CD8+ T 细胞的细胞因子产物激活肺泡巨噬细胞 体外对Pc的吞噬和杀伤作用； (2)判断是否有CD8+T细胞 对单独的 Pc 或与肺泡巨噬细胞联合具有细胞毒性 体外; (3)测定Pc免疫增加CD8+T的能力 细胞反应并减少体内感染； (4)确定能力 Pc 诱导的 CD8+ T 细胞的转移以调节体内感染。