Immunosuppression by mycobacterial arabinomannan

The means by which mycobacteria elude host defence mechanisms to cause human disease is unknown. This report provides the initial demonstration of a soluble product of Mycobacterium tuberculosis with immunosuppressive activity which may contribute to the pathogenicity of this organism. Mycobacterial D-arabino-D-mannan (AM), purified from culture filtrates of M. tuberculosis by Concanavalin A-Sepharose affinity chromatography did not itself induce ³H-thymidine incorporation or migration inhibitory factor production by peripheral blood mononuclear cells from tuberculin skin-test-positive healthy humans although it produced weak delayed skin-test reactions in these subjects. However, this mycobacterial cell wall polysaccharide suppressed the response of human lymphocytes to mycobacterial and other antigens as assessed with these in vitro correlates of delayed hypersensitivity. Immunosuppression by arabinomannan was not contingent upon prior exposure of the individual to M. tuberculosis, since it occurred with lymphocytes from tuberculin skin-test non-reactive as well as reactive subjects. Nor was it due to cytotoxicity, an antimitotic effect of the polysaccharide preparation or generation of suppressor cells. Rather, AM seemed to suppress macrophage-dependent, antigen-induced activation of human lymphocytes. This immunosuppressive substance elaborated by mycobacteria has potential relevance to the pathogenesis of human tuberculosis and the nature and limitation of the resulting host response.