Infection with live mycobacteria inhibits in vitro detection of Ia antigen on macrophages.

Both antigen-specific and non-specific anergy are common features of disseminated mycobacterial infections, and the pathogenesis of such anergy is as yet not fully understood. To date, most studies have focused on the efferent limb of the immune response, and no detailed information is available on the early macrophage-T cell interaction and its consequence on T cell clonal proliferation. To gain information on this crucial phase of mycobacteriosis, we have conducted studies to evaluate the effect of M. kansasii infection on Ia expression induced by T cell-derived lymphokine and have assessed whether such cells can adequately present either mycobacterial or allogeneic antigens to T cells. In vitro infection of mouse resident peritoneal macrophages with live but not heat-killed M. kansasii resulted in a significantly reduced percentage of cells expressing monoclonal antibody detectable Ia antigen following optimal stimulation with crude lymphokine preparations or recombinant mouse gamma interferon. In parallel experiments, macrophages infected with the mycobacteria were co-cultured with syngeneic in vivo M. kansasii sensitized non-adherent, nylon-wool purified lymph node cells, and lymphoproliferation was measured by [3H]thymidine incorporation. It was shown that in co-cultures with macrophages infected with live M. kansasii, the lymphocyte proliferation was marked even in very low infection ratios. In contrast, the response to heat-killed bacilli was dose dependent, reaching peak levels only in high infection ratios. The ability of infected macrophages to present allogeneic antigens was assessed using the mixed leukocyte reaction. Macrophages infected with heat-killed M. kansasii were able to induce a mixed leukocyte reaction similar to uninfected macrophages whereas macrophages infected with live M. kansasii were unable to stimulate allogeneic T cells. These findings may have implications on immunological disturbances often seen in mycobacterial infections, such as leprosy, in which there can be large numbers of non-toxic viable intracellular bacilli.