A model on the influence of age on immunity to infection with Mycobacterium tuberculosis.

Increasing susceptibility of the elderly to many infectious diseases is highly associated with the loss or delay in the generation of antigen-specific CD4(+) T cells. For Mycobacterium tuberculosis infection, where antigen-specific CD4(+) T cell derived IFN-gamma is essential, such a loss can lead to a significant failure to control infection. The present paper develops a mathematical model of infection with M. tuberculosis in old mice. The model includes an early resistance to infection which is mediated by CD8(+) T cells. A subsequent reversal of this phenotype results from the slow generation of CD4(+) T cell mediated immunity in old age. The model simulations corroborate experimental data and hence, the model was used to test whether immunity to infection could be improved in old mice, if CD4(+) T cell responses were enhanced. Our simulations indicate that boosting antigen presentation and T cell proliferation can decrease the M. tuberculosis burden in the lung.