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-γ production

The lungs of naı¨ve 18-month-old mice contain an abundant resident population of CD8 T cells that express typical markers of memory, express elevated levels of Th1 cytokine receptors on their surface, and are capable of non-specific IFN-γ production in response to a Th1 cytokine cocktail. In this study we characterize this population of CD8 T cells in the lungs and spleens of mice with increasing age. In general, the proportion of CD8 T cells expressing markers of memory and Th1 cytokine receptors increased with age. The enhanced ability of CD8 T cells to produce IFN-γ in an antigen independent manner followed this pattern as well, beginning to increase between 6 and 12 months of age. Interestingly, the phenotypic and functional age-related changes in CD8 T cells were also associated with a progressive age-related increase in early resistance to Mycobacterium tuberculosis. Taken together, these data suggest that as mice age a population of memory CD8 T cells, that are capable of contributing to innate immune responses to M. tuberculosis, gradually emerges and could be relevant for developing strategies to enhance immunity in the elderly.