Characterization and anti-tuberculosis effects of γδ T cells expanded and activated by <i>Mycobacterium tuberculosis</i> heat-resistant antigen

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a severe threat to human health. A variety of highly immunogenic tuberculosis proteins have been used as targets in vaccine development to mitigate the spread of TB. Although Th1-type immunity has long been considered a crucial part of resistance to Mtb, γδ T cells, the predominant source of IL-17, are not negligible in controlling the early stages of TB infection. In addition to classical phosphoantigens, Mycobacterium tuberculosis heat-resistant antigens (HAg), a complex containing 564 proteins obtained from live tuberculosis bacteria after heat treatment at 121 °C for 20 min, have been confirmed to be highly effective γδ T cell stimulators as well. Several studies have demonstrated that HAg-activated γδ T cells can participate in TB immunity by secreting multiple cytokines against Mtb or by interacting with other innate immune cells. In this review, we present a possible mechanism of HAg stimulation of γδ T cells and the role of HAg-activated γδ T cells in anti-TB immunity. We also highlight the limitations of studies on HAg activation of γδ T cells and suggest further research directions on the relationship between HAg and γδ T cells.