CD8-and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis

The role of CD8 T lymphocytes in the immune response to Mycobacterium tuber culosis infection remains enigmatic, with persuasive reports of both cytoly tic and noncytolytic (cytokine-mediated) responses to infection, To address the importance of the cytolytic mechanisms, mice with targeted disruptions for CD8 and perforin or with gene mutations in the CD95/ CD95L signaling p athway were exposed to pulmonary infection. All mice tested showed no diffe rences in their ability to contain the growth of infection during the early phase of disease. As the chronic phase of the disease ensued, however, bot h CD8- and CD95/CD95L-deficient mice gradually lost their ability to limit bacterial growth. This was associated with a tendency toward pyogenic infla mmation in the lung. This tendency was not seen in the perforin gene-disrup ted mice. In CD8 gene-disrupted mice, the ability to generate interferon-ga mma secreting T cells was unimpaired. Although these cells were capable of entering the lung they were unable to influence the increasing bacterial lo ad in this organ.