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  • Title: Peripheral loss of CD8(+) CD161(++) TCRVα7·2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients.
    Author: Barathan M, Mohamed R, Vadivelu J, Chang LY, Saeidi A, Yong YK, Ravishankar Ram M, Gopal K, Velu V, Larsson M, Shankar EM.
    Journal: Eur J Clin Invest; 2016 Feb; 46(2):170-80. PubMed ID: 26681320.
    Abstract:
    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.
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