CD8 T cells and immunity to tuberculosis in old mice

描述(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，为这一人群接种疫苗的效果较差。要设计一种疫苗或暴露后疗法来保护老年人免受传染病的侵袭，首先必须了解当老年人遇到病原体时，它与年轻人的免疫反应有何不同。利用衰老的小鼠结核病模型，我们发现老年小鼠对感染表现出短暂的早期抵抗力，这种抵抗力与肺内CD8 T细胞的存在有关。这确定了一种以前未被认识到的老年小鼠的新免疫机制，这种机制显然不存在于幼鼠的肺中。因此，CD8T细胞可能是为老年人设计疫苗或新的暴露后疗法的潜在目标人群。利用低剂量的结核气溶胶感染模型，我们将通过确定老年小鼠肺内CD8T细胞何时变得更加活跃以及CD8T细胞介导早期耐药的机制来进一步表征这种CD8T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老化小鼠群体中的旧野生型、基因中断或转基因小鼠。这些技术方法将结合使用流式细胞术、免疫组织化学染色和实时聚合酶链式反应，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.