γδ T cells, both human and murine, have been found to be highly responsive to mycobacterial antigens. However, the role and function of γδ T cells in the immune response to Mycobacterium tuberculosis remain largely unknown. In earlier studies, we demonstrated that monocytes infected with live M. tuberculosis were particularly effective inducers of human peripheral blood γδ T cells. The present studies were performed to further characterize the interaction between human mononuclear phagocytes, γδ T cells, and live M. tuberculosis, in comparison with CD4+ T cells. First, we found that resting γδ T cells expanded in vitro by live M. tuberculosis were specific for M. tuberculosis, and that heat killing and washing the mycobacteria removed the antigen(s) for γδ T cells. In contrast, the heat- killed mycobacteria retained significant antigenicity for CD4+ T cells. Second, live M. tuberculosis-expanded γδ T cells from healthy tuberculin- positive donors did not respond significantly to the antigens in M. tuberculosis culture filtrate, including the 65- and 71-kDa mycobacterial heat shock proteins. Third, the activation of γδ T cells by live mycobacteria was dependent on antigen-presenting cells, and mononuclear phagocytes were found to be very efficient antigen-presenting cells both for resting peripheral blood γδ T cells and for activated expanded γδ T cells. The mononuclear phagocyte carried the necessary costimulatory factors necessary for γδ T-cell proliferation. Fourth, the antigen repertoire and HLA requirements for CD4+ memory T cells and those for γδ T cells appear to be quite distinct from each other. CD4+ T cells recognized both soluble protein antigens and whole organisms in a class II major histocompatibility complex-restricted manner, whereas γδ T cells appeared to recognize only constituents associated with the whole organism and were not restricted by class I or class II major histocompatibility complex molecules. Finally, the assay system described to expand and purify responding CD4+ and γδ T cells after stimulation with live M. tuberculosis represented a simple approach to the direct comparison of these two T-cell populations in the interaction with mononuclear phagocytes infected with M. tuberculosis. Such studies provide insight not only into the relative roles of human CD4+ and γδ T cells in the human immune response to intracellular bacterial pathogens such as M. tuberculosis but also into the basic biologic role of human γδ T cells in antimicrobial immunity.
|Original language||English (US)|
|Number of pages||9|
|Journal||Infection and Immunity|
|State||Published - 1992|
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