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Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
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2015 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 45, no 5, 466-474 p.Article in journal (Refereed) Published
Abstract [en]

BackgroundHepatitis C virus (HCV) causes persistent disease in similar to 85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses. Materials and methodsWe characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin. ResultsHCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells. ConclusionsChronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.

Place, publisher, year, edition, pages
Wiley , 2015. Vol. 45, no 5, 466-474 p.
Keyword [en]
CD38; CD57; HCV infection; IL-7R; immunosenescence; PD-1
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-118864DOI: 10.1111/eci.12429ISI: 000353965300004PubMedID: 25721991OAI: oai:DiVA.org:liu-118864DiVA: diva2:817972
Note

Funding Agencies|High Impact Research (HIR); University of Malaya [UM.C.625/1/HIR/139]; University Malaya Fellowship Scheme; Swedish Research Council [AI52731]; Swedish Physicians Against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; Linkoping University Hospital Research Fund; Swedish Society of Medicine (Svenska Lakaresallskapet)

Available from: 2015-06-08 Created: 2015-06-04 Last updated: 2015-06-08

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Larsson, Marie
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Division of Microbiology and Molecular MedicineFaculty of Health Sciences
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ReferencesLink to record
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