Immunologic aspects of mycobacterial infections.
Immunosuppressive mechanisms loom as important factors in depression of delayed-type hypersensitivity responses during active tuberculosis. Nonspecific suppression may be mediated by circulating immune complexes containing mycobacterial polysaccharides such as D-arabino-D-galactan. The mechanism of suppression involves activation of monocyte production of immunosuppressive prostaglandin E2. Peripheral blood mononuclear cells from patients with tuberculosis include increased numbers of monocytes that suppress the response to tuberculin purified protein derivative (PPD). Antigen-specific suppression is associated with monocyte activation by a number of criteria, including decreased surface expression of HLA-DR determinants and increased production of interleukin 1 (IL-1). The increased production of IL-1 is associated with--and may have a causal relation to--immunosuppression. A second parallel regulatory mechanism involves PPD-specific suppression by Fc gamma receptor-bearing lymphocytes. The consequence of these immunosuppressive circuits is depression of tuberculin-induced blastogenesis, production of IL-2, and generation of IL-2 receptors. These findings suggest that natural infection with Mycobacterium tuberculosis may result in immunosuppression. Studies of potentially protective antigens in experimental systems must be designed to assess and avoid activation of suppressor circuits.
Ellner
J J
JJ
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
Wallis
R S
RS
D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000032:analysis; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000939:Epitopes