The influence of age on immunity to infection with Mycobacterium tuberculosis

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Abstract
Changes within the immune system during aging lead to an elderly population that is both highly susceptible to infectious diseases and unresponsive to typical vaccine protocols. Using the murine model of tuberculosis, we have identified key differences in the generation of T-helper 1 cell immunity between old and young mice, and this information may be important for the design of new vaccines or post exposure therapies to protect the elderly against infectious diseases. In response to infection with Mycobacterium tuberculosis, it has been shown that the generation of antigen-specific CD4(+) T-cell immunity is impaired in old mice. In contrast, recent findings document that old mice display a transient enhanced resistance that occurs within the first 3 weeks of infection. Early resistance was associated with the presence of CD8(+) T cells and their ability to produce interferon-gamma (IFN-gamma) well before their young counterparts. Further investigation into the mechanism by which CD8(+) T cells are induced to secrete IFN-gammain vivo could provide an approach to enhance the effector function of these cells and subsequently protect elderly individuals from respiratory pathogens such as M. tuberculosis.