Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors

Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels o...

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Main Authors: Jaisheela Vimali, Yean K. Yong, Amudhan Murugesan, Hong Y. Tan, Ying Zhang, Rajeev Ashwin, Sivadoss Raju, Pachamuthu Balakrishnan, Marie Larsson, Vijayakumar Velu, Esaki M. Shankar
Format: Article
Language:English
Published: IMR Press 2024-03-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903128
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author Jaisheela Vimali
Yean K. Yong
Amudhan Murugesan
Hong Y. Tan
Ying Zhang
Rajeev Ashwin
Sivadoss Raju
Pachamuthu Balakrishnan
Marie Larsson
Vijayakumar Velu
Esaki M. Shankar
author_facet Jaisheela Vimali
Yean K. Yong
Amudhan Murugesan
Hong Y. Tan
Ying Zhang
Rajeev Ashwin
Sivadoss Raju
Pachamuthu Balakrishnan
Marie Larsson
Vijayakumar Velu
Esaki M. Shankar
author_sort Jaisheela Vimali
collection DOAJ
description Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.
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spelling doaj.art-2f98be5fc91a4c09ba99fc0f5d0205c02024-03-28T02:27:55ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-03-0129312810.31083/j.fbl2903128S2768-6701(24)01249-8Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory ReceptorsJaisheela Vimali0Yean K. Yong1Amudhan Murugesan2Hong Y. Tan3Ying Zhang4Rajeev Ashwin5Sivadoss Raju6Pachamuthu Balakrishnan7Marie Larsson8Vijayakumar Velu9Esaki M. Shankar10Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu, 610005 Thiruvarur, IndiaLaboratory Centre, Xiamen University Malaysia, 43900 Sepang, Selangor, MalaysiaDepartment of Microbiology, Government Theni Medical College and Hospital, 625512 Theni, IndiaSchool of Traditional Chinese Medicine, Xiamen University Malaysia, 43900 Sepang, Selangor, MalaysiaChemical Engineering, Xiamen University Malaysia, 43900 Sepang, Selangor, MalaysiaInfection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu, 610005 Thiruvarur, IndiaState Public Health Laboratory, Directorate of Public Health and Preventive Medicine, DMS Campus, 600018 Teynampet, Chennai, IndiaCenter for Infectious Diseases, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, 602105 Chennai, Tamil Nadu, IndiaDivision of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, SwedenDepartment of Pathology and Laboratory Medicine, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USAInfection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu, 610005 Thiruvarur, IndiaBackground: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903128hbvhivmait cellspd-1t cell exhaustion
spellingShingle Jaisheela Vimali
Yean K. Yong
Amudhan Murugesan
Hong Y. Tan
Ying Zhang
Rajeev Ashwin
Sivadoss Raju
Pachamuthu Balakrishnan
Marie Larsson
Vijayakumar Velu
Esaki M. Shankar
Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
Frontiers in Bioscience-Landmark
hbv
hiv
mait cells
pd-1
t cell exhaustion
title Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
title_full Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
title_fullStr Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
title_full_unstemmed Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
title_short Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
title_sort chronic viral infection compromises the quality of circulating mucosal associated invariant t cells and follicular t helper cells via expression of inhibitory receptors
topic hbv
hiv
mait cells
pd-1
t cell exhaustion
url https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903128
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