T CELL RESPONSES TO INTRACELLULAR BACTERIAL PATHOGENS

描述(改编自调查者摘要)：有 对了解宿主免疫的作用很感兴趣 清除传染病病原体时的反应。这样的信息是 与疾病过程的理解和 制定有效的疫苗策略。此外，这样的研究可以 提供对先前暴露于 一种感染性病原体与自身免疫性疾病的发展有关。 该项目描述了旨在识别和表征 感染猪瘟病毒后产生的特异性CD8+T细胞反应 革兰氏阴性肠道病原菌鼠伤寒沙门氏菌。初步 在小鼠模型中产生的数据表明： 用鼠伤寒沙门氏菌系统挑战，小鼠产生强大的 针对沙门氏菌感染细胞的CD8+T细胞反应。这 反应是CD8依赖的，可以识别H-2非... 受限制的时尚。此外，MHC的非限制性成分 沙门氏菌特异性CD8 T细胞应答识别靶标 依附时尚。根据初步数据，以下是 提出了具体的研究目标：1.沙门氏菌的特性 活体攻击小鼠伤寒沙门氏菌后的CD8+CTL。 2.检测CD8+CTL在限制毒力中的作用 沙门氏菌感染。3.表征和鉴定 沙门氏菌特异性CTL识别的表位。4.设计和评估 针对沙门氏菌表位的疫苗接种策略可能会引起 对强毒鼠伤寒沙门氏菌攻击的保护性免疫。这 信息将影响我们对CD8+T细胞作用的理解 在对主要病原体家族(革兰氏)的保护性免疫反应中 阴性菌)，也有助于设计有效的疫苗 能够诱导对肠道病原体的长期保护性免疫。 此外，这样的研究可能有助于自我认同 与细菌抗原发生交叉反应的蛋白质可能在 自体免疫过程的诱导。

DESCRIPTION (Adapted from the Investigator's abstract): There is considerable interest in understanding the role of the host immune response in the clearance of an infectious agent. Such information is relevant to the understanding of disease processes and to the development of effective vaccine strategies. Moreover, such studies can provide basic insights into the mechanisms by which prior exposure to an infectious agent is linked to the development of autoimmune disease. This project describes studies designed to identify and characterize the specific CD8+ T-cell response generated following infection with the Gram negative enteric pathogen, Salmonella typhimurium. Preliminary data have been generated in a murine model demonstrating that following system challenge with Salmonella typhimurium, mice generate a potent CD8+ T-cell response specific for Salmonella-infected cells. This response is CD8 dependent and can recognize targets in a H-2 non- restricted fashion. Furthermore, the non-MHC restricted component of the Salmonella specific CD8 T-cell response recognize targets in a Tap dependent fashion. Based on the preliminary data, the following Specific Aims are proposed: 1. Characterization of Salmonella-specific CD8+ CTLs following in vivo challenge with live virulent S. typhimurium. 2. Examination of the contribution of CD8+ CTLs in limiting virulent Salmonella infections. 3. Characterization and identification of epitopes recognized by Salmonella-specific CTLs. 4. Design and evaluate vaccination strategies targeting Salmonella epitopes that could evoke protective immunity to a challenge with virulent S. typhimurium. This information will impact on our understanding of the role of CD8+ T-cells in the protective immune response to a major family of pathogens (Gram- negative bacteria) and also aid in the design of effective vaccines capable of inducing long-term protective immunity to enteric pathogens. In addition, such studies may facilitate the identification of self proteins cross-reactive with bacterial antigens that may play a role in the induction of autoimmune processes.