Peripheral loss of CD8+ CD161++ TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients.

Background Mucosal-associated invariant T ( MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus ( HCV) infection remains unclear. Materials and methods We investigated the frequency of CD8⁺ CD161⁺⁺ TCR Vα7.2⁺ MAIT cells in a cross-sectional cohort of chronic HCV-infected patients ( n = 25) and healthy controls ( n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing ( CCR5 and CD103), biomarkers of immune exhaustion ( PD-1, TIM-3 and CTLA-4), chronic immune activation ( CD38 and HLA- DR), and immunosenescence ( CD57) by flow cytometry. Results The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA- DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. Conclusions Immune exhaustion and senescence of CD8⁺ CD161⁺⁺ TCR Vα7.2⁺ MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression. [ABSTRACT FROM AUTHOR]