Functions of T-cell subsets and cytokines in mycobacterial infections.
Phagocytosed M. tuberculosis either multiply inside the endocytic compartment of mononuclear phagocytes or they are destroyed by the host cell. Due to this macrophage-shelter (ab)used by mycobacteria, tuberculosis is controlled by the cellular immune response. Protection against mycobacteria depends on alpha/beta T-cells expressing the CD4 or CD8 phenotype. T-cell-mediated immunity amplifies macrophage capacities to kill and digest the bacilli. Specific alpha/beta T-cells produce several cytokines that attract and activate macrophages and additional lymphocytes, such as: interferon-gamma (IFN-gamma) which has the capacity to activate several antimicrobial properties of macrophages; tumour necrosis factor-alpha (TNF-alpha) a key cytokine involved in granuloma formation; interleukins 2, 6 and 8 (IL-2; IL-6 and IL-8); and interleukin 12 (IL-12), a candidate cytokine for the induction of Th1 cells. Furthermore, CD4+ and CD8+ T-cells display cytotoxic activity, which permits them to control mycobacterial growth through destruction of the infected cells. Escaping bacteria are subsequently ingested and destroyed by surrounding macrophages activated by T-cells. There is evidence to associate gamma/delta T-cells with antimycobacterial immunity, such as their preferential accumulation in inflammatory lesions, in necrotic areas of tuberculous lymphadenitis, and potent in vitro stimulation by M. tuberculosis components. In addition, M. tuberculosis activated gamma/delta T-cells are cytolytic and secrete several cytokines. Hence, clinical tuberculosis is associated with T-cell reactivity which controls the local concentrations of tubercle bacilli. Taken together, the cellular response, cytokine regulation, and the definition of target molecules are important aspects for the understanding of pathological immune mechanisms in tuberculosis.
Munk
M E
ME
Dept of Immunology, University of Ulm, Germany.
Emoto
M
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D009164:Mycobacterium Infections / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D016207:Cytokines