FUNCTIONS OF T-CELL SUBSETS AND CYTOKINES IN MYCOBACTERIAL INFECTIONS

Phagocytosed M. tuberculosis either multiply inside the endocytic comp artment of mononuclear phagocytes or they are destroyed by the host ce ll, Due to this macrophage-shelter (ab)used by mycobacteria, tuberculo sis is controlled by the cellular immune response. Protection against mycobacteria depends on alpha/beta T-cells expressing the CD4 or CD8 p henotype. T-cell-mediated immunity amplifies macrophage capacities to kill and digest the bacilli, Specific alpha/beta T-cells produce sever al cytokines that attract and activate macrophages and additional lymp hocytes, such as: interferon-gamma (IFN-gamma) which has the capacity to activate several antimicrobial properties of macrophages; tumour ne crosis factor-alpha (TNF-alpha) a key cytokine involved in granuloma f ormation; interleukins 2, 6 and 8 (IL-2; IL-6 and IL-8); and interleuk in 12 (IL-12), a candidate cytokine for the induction of Th1 cells. Fu rthermore, CD4+ and CD8+ T-cells display cytotoxic activity, which per mits them to control mycobacterial growth through destruction of the i nfected cells, Escaping bacteria are subsequently ingested and destroy ed 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 necrot ic 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, Henc e, clinical tuberculosis is associated with T-cell reactivity which co ntrols the local concentrations of tubercle bacilli, Taken together, t he cellular response, cytokine regulation, and the definition of targe t molecules are important aspects for the understanding of pathologica l immune mechanisms in tuberculosis.