T-CELL-DERIVED IL-10 ANTAGONIZES MACROPHAGE FUNCTION IN MYCOBACTERIALINFECTION

Pathogenic mycobacteria survive within macrophages despite T cell resp onses that activate host defenses against most pathogens. Among cytoki nes produced by T cells, IL-10 is known to negatively regulate Th1 cel ls as well as macrophages. IL-10 has been shown to inhibit the anti-my cobacterial activity of macrophages in vitro and could account for the ability of mycobacteria to survive intracellularly. To test the inhib itory functions of IL-10 in vivo, transgenic mice that secrete IL-10 f rom the T cell compartment were constructed and infected with Calmette -Guerin bacillus (Mycobacterium bovis), These mice were unable to clea r the infection and developed large bacterial burdens, Nonetheless, th eir T cells produced abundant amounts of IFN-gamma and IL-2 in respons e to Ag challenge, These results indicate that the presence of excess IL-10 had little, if any, effect on T cell function or development dur ing the immune response to Calmette-Guerin bacillus, Rather, the data suggest that IL-10 helps maintain mycobacterial infections by acting p rimarily at the level of the macrophage, overriding anti-mycobacterial signals delivered by IFN-gamma.