γδ T cells and mycobacterium tuberculosis

Mycobacterium tuberculosis remains one of the most common causes of morbidity and mortality of man, and is estimated to have infected approximately one third of the world's population [65]. Tubercle bacilli are spread most commonly from person to person by inhalation of aerosolized mycobacteria [66]. In the majority of infected individuals, natural and acquired immune responses are activated and successfully control M. tuberculosis[15]. Natural immune mechanisms - macrophages, NK cells, neutrophils - likely have an important role in the primary response to M. tuberculosis and may suffice to control infection in some individuals. However, acquired immune responses are necessary for control of M. tuberculosis infection in the majority of individuals. A positive tuberculin skin test (PPD) is the only evidence in these individuals for prior M. tuberculosis infection. Granulomas, consisting of activated macrophages fused into multinucleated giant cells surrounded by T cells, are the pathologic hallmark of protective immunity to M, tuberculosis and are regulated by T cells. Studies in animal models and in humans with cellular immune deficiencies have established clearly that T cells are critical for protective im mu ni ty to M. tuberculosis both as regulatory and effector cells (reviewed in [60]). Studies in the last ten years have determined that multiple T-cell subsets are activated by mycobacterial antigens, including CD+ alpha beta TCR+, CD8(+) alpha beta TCR+, gamma delta TCR+ and CD1-restricted alpha beta TCR+ T cells. The central role of CD4(+) T cells both as effector and regulatory cells in human protective immunity to M. tuberculosis is well established. However, the relative importance and role of the other T-cell subsets, and their relationship to CD4(+)T cells in the immune response to M. tuberculosis remain still largely undefined. Soon after genetic and biochemical proof for a distinct gamma delta TCR-bearing T-cell subset was provided, functional and phenotypic studies in murine models and humans suggested that ya T cells were activated in response to mycobacteria. These early observations have continued to prompt numerous investigators to attempt to further define the role of ya T cells in mycobacterial immunity and the manner in which ya T cells are activated by bacterial pathogens such as M. tuberculosis. Substantial progress has been made in clarifying the role of gamma delta T cells in M. tuberculosis infection since the last major reviews on this subject [30, 64].