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 me...

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Main Authors: Barathan, M., Mohamed, R., Vadivelu, J., Chang, L.Y., Saeidi, A., Yong, Y.K., Ravishankar Ram, M., Gopal, K., Velu, V., Larsson, M., Shankar, E.M.
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Published: Blackwell Publishing 2016
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author Barathan, M.
Mohamed, R.
Vadivelu, J.
Chang, L.Y.
Saeidi, A.
Yong, Y.K.
Ravishankar Ram, M.
Gopal, K.
Velu, V.
Larsson, M.
Shankar, E.M.
author_facet Barathan, M.
Mohamed, R.
Vadivelu, J.
Chang, L.Y.
Saeidi, A.
Yong, Y.K.
Ravishankar Ram, M.
Gopal, K.
Velu, V.
Larsson, M.
Shankar, E.M.
author_sort Barathan, M.
collection UM
description 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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spelling um.eprints-184632017-12-07T01:53:33Z http://eprints.um.edu.my/18463/ Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients Barathan, M. Mohamed, R. Vadivelu, J. Chang, L.Y. Saeidi, A. Yong, Y.K. Ravishankar Ram, M. Gopal, K. Velu, V. Larsson, M. Shankar, E.M. R Medicine 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. Blackwell Publishing 2016 Article PeerReviewed Barathan, M. and Mohamed, R. and Vadivelu, J. and Chang, L.Y. and Saeidi, A. and Yong, Y.K. and Ravishankar Ram, M. and Gopal, K. and Velu, V. and Larsson, M. and Shankar, E.M. (2016) Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients. European Journal of Clinical Investigation, 46 (2). pp. 170-180. ISSN 0014-2972, DOI https://doi.org/10.1111/eci.12581 <https://doi.org/10.1111/eci.12581>. https://doi.org/10.1111/eci.12581 doi:10.1111/eci.12581
spellingShingle R Medicine
Barathan, M.
Mohamed, R.
Vadivelu, J.
Chang, L.Y.
Saeidi, A.
Yong, Y.K.
Ravishankar Ram, M.
Gopal, K.
Velu, V.
Larsson, M.
Shankar, E.M.
Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title_full Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title_fullStr Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title_full_unstemmed Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title_short Peripheral loss of CD8+CD161++TCRVα7·2+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
title_sort peripheral loss of cd8 cd161 tcrvα7·2 mucosal associated invariant t cells in chronic hepatitis c virus infected patients
topic R Medicine
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