Clinical and experimental immunology
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Clin. Exp. Immunol. · Sep 2012
ReviewIs interferon-gamma the right marker for bacille Calmette-Guérin-induced immune protection? The missing link in our understanding of tuberculosis immunology.
Bacille Calmette-Guérin (BCG), developed a century ago, is the only licensed tuberculosis (TB) vaccine in use to date. The protective efficacy of BCG against TB varies with no apparent protection in some population, and mechanisms of its immune protection is poorly known, and yet BCG is the most widely used vaccine, with more than 4 billion BCG-vaccinated children globally. BCG is probably the only licensed vaccine currently in use believed to mediate immune protection through the production of interferon (IFN)-γ by CD4 T cells, which in turn activates macrophages to kill Mycobacterium tuberculosis (Mtb). ⋯ These studies point to the fact that there is a missing link in our understanding of TB immunology. Conversely, there is emerging evidence that other T cell subsets (gammadelta, γδ), CD8(+) T cells and natural killer (NK) cells may play a vital role in immune protection against Mtb infection and BCG-induced immune protection. γδ T cells and NK cells, which were considered to be part of the innate immunity in the past, have been shown to develop immunological memory upon re-encounter with the same pathogen. In this paper, the controversy over the role of IFN-γ as a marker for protective immunity against TB, and emerging data on the role of γδ T cells, CD8(+) and NK cells in TB immunology, will be presented.