CD8 T Cells and Immunity to Tuberculosis in Old Mice

描述（由申请人提供）：老年人更容易感染许多传染病，但当使用为年轻人设计的疫苗时，对这一人群接种疫苗的效果较差。为了设计一种可以保护老年人免受感染性疾病的疫苗或暴露后治疗，首先需要了解当遇到病原体时，衰老的免疫反应与年轻人的免疫反应有何不同。使用老化的结核病小鼠模型，我们发现老年小鼠表达对感染的短暂早期抵抗力，这与肺内CD 8 T细胞的存在相关。这在老年小鼠中发现了一种以前未被认识到的新免疫机制，而这种机制在年轻小鼠的肺中显然不存在。因此，CD 8 T细胞可能是为老年人设计疫苗或新型暴露后治疗的潜在目标群体。使用结核病的低剂量气溶胶感染模型，我们将通过确定CD 8 T细胞何时在老年小鼠的肺内变得更活跃以及CD 8 T细胞介导早期抗性的机制来进一步表征该CD 8 T细胞群体。研究将在科罗拉多州立大学的一个新的BSL-3设施中进行，并将使用来自我们现有的内部老化小鼠群的旧野生型、基因破坏或转基因小鼠。技术方法将使用流式细胞术，免疫组织化学染色和实时PCR的组合，以解决拟议的目标。

DESCRIPTION (provided by applicant): The elderly are more susceptible to many infectious diseases, and yet vaccinating this population is less effective when vaccines that are designed for young individuals are used. To design a vaccine or post-exposure therapy that can protect the elderly against infectious disease it is first necessary to understand how the aging immune response differs from younger individuals when it encounters a pathogen. Using the aging mouse model of tuberculosis we have found that old mice express a transient early resistance to infection that correlates with the presence of CD8 T cells within the lungs. This identifies a previously unrecognized novel immune mechanism in old mice that is clearly absent from the lungs of young mice. The CD8 T cell may therefore be a potential target population for the design of vaccines or novel post-exposure therapies for the elderly. Using the low dose aerosol infection model of tuberculosis we will characterize this CD8 T cell population further by determining when CD8 T cells become more active within the lungs of old mice and the mechanism by which CD8 T cells mediate early resistance. Studies will be carried out in a new BSL-3 facility at Colorado State University and will use old wild type, gene-disrupted, or transgenic mice from our existing in-house aging mouse colonies. The technical approaches will use a combination of flow cytometry, immuno-histochemical staining, and real-time PCR, to address the proposed aims.