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，然而，当使用为年轻人设计的疫苗时，为这一人群接种疫苗的效果较差。为了设计一种能够保护老年人免受传染病侵害的疫苗或暴露后疗法，首先有必要了解老年人在遇到病原体时的免疫反应与年轻人有何不同。使用衰老小鼠结核病模型，我们发现老年小鼠对感染表现出短暂的早期抵抗，这与肺内CD8 T细胞的存在有关。这在老年小鼠中发现了一种以前未被认识到的新型免疫机制，这种机制在年轻小鼠的肺部显然是不存在的。因此，CD8 T细胞可能是设计疫苗或针对老年人的新型暴露后疗法的潜在目标群体。利用结核病的低剂量气溶胶感染模型，我们将通过确定CD8 T细胞何时在老年小鼠的肺部变得更活跃以及CD8 T细胞介导早期耐药性的机制来进一步表征CD8 T细胞群。研究将在科罗拉多州立大学的一个新的BSL-3设施中进行，并将使用我们现有的内部衰老小鼠群体中的旧野生型，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相结合，以解决提出的目标。

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.