Aging and immunity to tuberculosis: increased susceptibility of old mice reflects a decreased capacity to generate mediator T lymphocytes

Abstract

This study employed an experimental mouse model of Mycobacterium tuberculosis infection to investigate the effects of aging on T cell-mediated protective cellular immunity. It was found that although mice of 3 to 18 mo of age were fully resistant to a standard immunizing dose of Mycobacterium tuberculosis, progressive mortality was observed in old (24 to 28 mo) mice. Death of these older animals was associated with an inability to contain or to eliminate the mycobacterial infection in the spleen and liver, and with an inability to prevent the progressive growth of the infection in the lungs. It was then revealed by the use of reciprocal passive cell transfer experiments that the age-related susceptibility of old mice reflected an inability to generate mediator protective T lymphocytes in response to the infection. In contrast, no evidence was obtained to indicate any defect at the effector cell (macrophage) level, as evidenced primarily by the finding that immune T cells from young mice conferred equivalent levels of immunity upon both old and young recipients. The results suggest therefore that T cell-mediated immunity undergoes an age-related decline in terms of its ability to respond to infection with Mycobacterium tuberculosis.