Cellular interactions in bovine tuberculosis:: release of active mycobacteria from infected macrophages by antigen-stimulated T cells

The outcome of Mycobacterium bovis infections depends on the interactions of infected macrophages with T lymphocytes. Several studies in humans and in mouse models have suggested an important role for cytotoxicity in the protective immune response to mycobacterial infections, and both CD4(+) and CD8(+) T cells have been shown to elicit appropriate cytolytic activity. The present study investigated in vitro interactions of T cells with M. bovis-infected macrophages in bovine tuberculosis. The results showed that following interaction with antigen-stimulated peripheral blood mononuclear cells (PBMC) from infected cattle, there was an increased presence of M, bovis in the extracellular compartment of infected macrophage cultures, as measured by incorporation of [H-3]uracil into mycobacterial RNA. Furthermore, out of a panel of T-cell clones from infected cattle, it was found that a higher proportion of CD8(+) clones produced an increase in the number of metabolically active extracellular M. bovis organisms compared with CD4(+) clones. Finally, a positive correlation between percentage of antigen-dependent release of mycobacteria and total uracil uptake by M. bovis within culture systems was detected. This could be regarded as an indication of preferential intracellular control of mycobacteria by activated macrophages.