The role of T cell--macrophage interactions in tuberculosis.
Acquired resistance against tuberculosis paradigmatically depends on specific T lymphocytes and mononuclear phagocytes. The etiological agent, Mycobacterium tuberculosis is capable of replicating in mononuclear phagocytes which act both as habitat and as effectors of protection. Upon interaction with antigen-specific T lymphocytes infected mononuclear phagocytes acquire tuberculostatic activities. Here, data from experimental tuberculosis studies in mice are summarized which show that: interleukins produced by cloned T cells and recombinant interferon-gamma are capable of activating tuberculostatic capacities in macrophages; both CD4 and CD8 T cells, after adequate stimulation, produce interferon-gamma; CD8 T cells lyse macrophages in an antigen-specific way; not only CD8 but also CD4 T cells possess an antigen-specific cytolytic potential; lysis of infected macrophages results in mycobacterial growth inhibition. Evidence is also presented that tuberculostatic activities of activated macrophages depend on phagosome-lysosome fusion and are independent of reactive oxygen metabolites and that some strains of M. tuberculosis are resistant against interferon-gamma activities macrophages. These findings suggest that both helper and cytolytic T cells participate in the immune response to tuberculosis and that similar T cell mechanisms contribute to resistance as well as pathogenesis. Protection against tuberculosis, therefore, depends on subtle coordination of the immune response.
Kaufmann
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SH
Department of Medical Microbiology and Immunology, University of Ulm, Federal Republic of Germany.
Flesch
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IE
D000818:Animals; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D007378:Interleukins / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
D007378:Interleukins