Increased effector γδ T cells with enhanced cytokine production are associated with inflammatory abnormalities in severe hand, foot, and mouth disease

Background: Although gamma delta T cells have been reported to be closely related to the immunopathogenesis of some viral infectious diseases, the changes or roles of gamma delta T cells in the development of hand, foot, and mouth disease (HFMD) remain unclear. Methods: Peripheral y8 T cells and their subsets were determined by surface (gamma delta TCR, V31 TCR, V82 TCR, CD45RA, and CD27) or intracellular (IFN-gamma, TNF-alpha, CD107a, and Granzyme B) markers in healthy controls (HCs) and HFMD patients with FACS. The plasma levels of IFN-gamma, TNF-alpha, IL-6, and MCP-1 were measured by ELISA. Differences in gamma delta T cells or their subsets and correlations between gamma delta T cells and inflammation indicators were statistically analyzed. Results: Compared to HCs, HFMD patients showed increased effector gamma delta T and TNF-alpha(+) gamma delta T cells and plasma TNF-alpha levels, especially in severe cases. In addition, significantly increased V delta 1 T and IFN-gamma(+) gamma delta T cells and other plasma inflammatory cytokines were further found in severe patients. Furthermore, EV71 + severe patients showed significantly increased effector and cytokine-producing gamma delta T cells, while the EV71- severe patients displayed significantly greater plasma cytokine levels. The percentage of IFN-gamma(+) gamma delta T or TNF-alpha(+) gamma delta T cells was positively correlated with that of effector y8 T cells. There was a positive correlation between the proportion of V delta 1 T cells and white blood cell (WBC) count or the proportion of IFN-gamma(+) gamma delta T or TNF-alpha(+) gamma delta T cells and neutrophil (N) count, while there was a negative correlation between V delta 2 T cells and WBC or N count. Moreover, the percentages of V delta 1 T and effector gamma delta T cells in the acute phase of disease declined significantly to normal levels during the recovery phase. Conclusions: Increased effector gamma delta T cells with enhanced cytokine production were remarkably observed in severe HFMD patients, which was also associated with clinical inflammation parameters. These data indicated that gamma delta T cells might be involved in inflammatory abnormalities in severe HFMD.