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.
|Rottinghaus, Erin K; Vesosky, Bridget; Turner, Joanne (2010) TLR-2 independent recognition of Mycobacterium tuberculosis by CD11c+ pulmonary cells from old mice. Mech Ageing Dev 131:405-14|
|Rottinghaus, Erin K; Vesosky, Bridget; Turner, Joanne (2009) Interleukin-12 is sufficient to promote antigen-independent interferon-gamma production by CD8 T cells in old mice. Immunology 128:e679-90|
|Vesosky, Bridget; Rottinghaus, Erin K; Davis, Craig et al. (2009) CD8 T Cells in old mice contribute to the innate immune response to Mycobacterium tuberculosis via interleukin-12p70-dependent and antigen-independent production of gamma interferon. Infect Immun 77:3355-63|
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|Vesosky, Bridget; Flaherty, David K; Rottinghaus, Erin K et al. (2006) Age dependent increase in early resistance of mice to Mycobacterium tuberculosis is associated with an increase in CD8 T cells that are capable of antigen independent IFN-gamma production. Exp Gerontol 41:1185-94|