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 o f infected macrophages with T lymphocytes. Several studies in humans and in mouse models have suggested an important role for cytotoxicity in the prot ective immune response to mycobacterial infections, and both CD4(+) and CD8 (+) T cells have been shown to elicit appropriate cytolytic activity. The p resent study investigated in vitro interactions of T cells with M. bovis-in fected macrophages in bovine tuberculosis. The results showed that followin g interaction with antigen-stimulated peripheral blood mononuclear cells (P BMC) from infected cattle, there was an increased presence of M, bovis in t he extracellular compartment of infected macrophage cultures, as measured b y 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 p roportion of CD8(+) clones produced an increase in the number of metabolica lly active extracellular M. bovis organisms compared with CD4(+) clones. Fi nally, a positive correlation between percentage of antigen-dependent relea se of mycobacteria and total uracil uptake by M. bovis within culture syste ms was detected. This could be regarded as an indication of preferential in tracellular control of mycobacteria by activated macrophages.