MAIT be different-persisting dysfunction after DAA-mediated clearance of chronic hepatitis C virus infection

MAIT cells are an abundant innate-like T-cell subset that is defined by the invariant T-cell receptor (iTCR) V-alpha chain Vα7.2-Jα33. Little is currently known about their frequency and function in chronic hepatitis C virus (HCV) infection and their fate after therapy-mediated HCV elimination by direct acting antivirals (DAA). In this issue of the European Journal of Immunology, Hengst et al. [Eur. J. Immunol. 2016. 46: 2204-2210] give important novel insights into the biological role of MAIT cells in a relevant human chronic viral infection by showing that first, MAIT cells are only present at low frequencies in chronic HCV infection; second, circulating MAIT cells in HCV patients also display an altered phenotype; third, they are impaired in their MR-1-dependent effector functions and finally, and maybe most importantly, MAIT-cell frequency and function was not restored after HCV elimination by DAA therapy. These results suggest that MAIT cells are severely affected by a chronic human viral infection in their frequency and function and that this impairment is not reversed after HCV elimination. This is in contrast to rapid DAA-mediated restorations of NK-cell and CD8(+) T-cell functions, and indicates a differential impact of chronic infection and clearance on different immune cell subsets.