In vitro T-cell activation of monocyte-derived macrophages by soluble messengers or cell-to-cell contact in bovine tuberculosis

The macrophage plays a dual role in tuberculosis, promoting not only protec tion against mycobacteria, but also survival of the pathogen. Macrophages i nhibit multiplication of mycobacteria but also act in concert with lymphocy tes through presentation of antigens to T cells. Studies in animal and huma n infections have suggested a correlation of in vitro growth rates of mycob acteria with in vivo virulence, using uracil uptake to assess mycobacterial metabolism. This study found that blood-derived, non-activated bovine macr ophages were capable of controlling Mycobacterium bovis bacillus Calmette-G uerin growth for up to 96 hr, but were permissive to intracellular growth o f virulent M. bovis. The present investigation compared the in vitro modula tion of these macrophage activities by cytokine-rich T-cell supernatants or cell-to-cell contact. On the one hand, treatment of cultured monocytes wit h mitogen-produced T-cell supernatants promoted morphological changes sugge stive of an activation status, enhanced the antigen presentation capabiliti es of monocytes and up-regulated major histocompatibility complex class II expression. However, this activation was not associated with enhanced anti- M. bovis activity. On the other hand, incubation of infected monocytes with T-cell populations resulted in proportionally increased inhibition of M. b ovis uracil uptake. This inhibition was also seen using cells from uninfect ed animals and indicated the necessity for cell-to-cell contact to promote antimycobacterial capability.