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Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chr...

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Main Authors: Yong, Yean K., Saeidi, Alireza, Tan, Hong Y., Rosmawati, Mohamed, Enström, Philip F., Al Batran, Rami, Vasuki, V., Chattopadhyay, Indranil, Murugesan, Amudhan, Vignesh, Ramachandran, Kamarulzaman, Adeeba, Rajarajeswaran, Jayakumar, Ansari, Abdul W., Vadivelu, Jamuna, Ussher, James E., Velu, Vijayakumar, Larsson, Marie, Shankar, Esaki Muthu
Format: Article
Published: Frontiers Media 2018
Subjects:
R Medicine
Online Access:http://eprints.um.edu.my/20260/
https://doi.org/10.3389/fimmu.2018.00472
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spelling my.um.eprints.202602019-02-12T01:43:01Z http://eprints.um.edu.my/20260/ Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection Yong, Yean K. Saeidi, Alireza Tan, Hong Y. Rosmawati, Mohamed Enström, Philip F. Al Batran, Rami Vasuki, V. Chattopadhyay, Indranil Murugesan, Amudhan Vignesh, Ramachandran Kamarulzaman, Adeeba Rajarajeswaran, Jayakumar Ansari, Abdul W. Vadivelu, Jamuna Ussher, James E. Velu, Vijayakumar Larsson, Marie Shankar, Esaki Muthu R Medicine Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1. Frontiers Media 2018 Article PeerReviewed Yong, Yean K. and Saeidi, Alireza and Tan, Hong Y. and Rosmawati, Mohamed and Enström, Philip F. and Al Batran, Rami and Vasuki, V. and Chattopadhyay, Indranil and Murugesan, Amudhan and Vignesh, Ramachandran and Kamarulzaman, Adeeba and Rajarajeswaran, Jayakumar and Ansari, Abdul W. and Vadivelu, Jamuna and Ussher, James E. and Velu, Vijayakumar and Larsson, Marie and Shankar, Esaki Muthu (2018) Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection. Frontiers in Immunology, 9. p. 472. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2018.00472 doi:10.3389/fimmu.2018.00472
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Yong, Yean K.
Saeidi, Alireza
Tan, Hong Y.
Rosmawati, Mohamed
Enström, Philip F.
Al Batran, Rami
Vasuki, V.
Chattopadhyay, Indranil
Murugesan, Amudhan
Vignesh, Ramachandran
Kamarulzaman, Adeeba
Rajarajeswaran, Jayakumar
Ansari, Abdul W.
Vadivelu, Jamuna
Ussher, James E.
Velu, Vijayakumar
Larsson, Marie
Shankar, Esaki Muthu
Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
description Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
format Article
author Yong, Yean K.
Saeidi, Alireza
Tan, Hong Y.
Rosmawati, Mohamed
Enström, Philip F.
Al Batran, Rami
Vasuki, V.
Chattopadhyay, Indranil
Murugesan, Amudhan
Vignesh, Ramachandran
Kamarulzaman, Adeeba
Rajarajeswaran, Jayakumar
Ansari, Abdul W.
Vadivelu, Jamuna
Ussher, James E.
Velu, Vijayakumar
Larsson, Marie
Shankar, Esaki Muthu
author_facet Yong, Yean K.
Saeidi, Alireza
Tan, Hong Y.
Rosmawati, Mohamed
Enström, Philip F.
Al Batran, Rami
Vasuki, V.
Chattopadhyay, Indranil
Murugesan, Amudhan
Vignesh, Ramachandran
Kamarulzaman, Adeeba
Rajarajeswaran, Jayakumar
Ansari, Abdul W.
Vadivelu, Jamuna
Ussher, James E.
Velu, Vijayakumar
Larsson, Marie
Shankar, Esaki Muthu
author_sort Yong, Yean K.
title Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
title_short Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
title_full Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
title_fullStr Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
title_full_unstemmed Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
title_sort hyper-expression of pd-1 is associated with the levels of exhausted and dysfunctional phenotypes of circulating cd161++tcr ivα7.2+ mucosal-associated invariant t cells in chronic hepatitis b virus infection
publisher Frontiers Media
publishDate 2018
url http://eprints.um.edu.my/20260/
https://doi.org/10.3389/fimmu.2018.00472
_version_ 1643691226597163008
score 13.211869

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