GrippeAllemagneV3, Main, Exploration, bibRecord, 000289

Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

Identifieur interne : 000289 ( Main/Exploration ); précédent : 000288; suivant : 000290

Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

Auteurs : Bijan Raziorrouh [Allemagne] ; Axel Ulsenheimer ; Winfried Schraut ; Malte Heeg ; Peter Kurktschiev ; Reinhart Zachoval ; Maria-Christina Jung ; Robert Thimme ; Christoph Neumann-Haefelin ; Sophia Horster ; Martin W Chtler ; Michael Spannagl ; Jürgen Haas ; Helmut M. Diepolder ; Norbert H. Grüner

Source :

Gastroenterology [ 1528-0012 ] ; 2011.

RBID : pubmed:21763239

Descripteurs français

English descriptors

KwdEn :
- Antibodies, Neutralizing, Antigens, CD (immunology), Antigens, CD (metabolism), Antigens, Surface (metabolism), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (virology), CTLA-4 Antigen (metabolism), Case-Control Studies, Cell Proliferation, Cells, Cultured, Female, Germany, Hepacivirus (genetics), Hepacivirus (immunology), Hepatitis C, Chronic (diagnosis), Hepatitis C, Chronic (immunology), Herpesvirus 4, Human (immunology), Humans, Interferon-gamma (metabolism), Interleukin-10 (immunology), Interleukin-10 (metabolism), Interleukin-2 (metabolism), Lymphocyte Activation, Male, Middle Aged, Orthomyxoviridae (immunology), Programmed Cell Death 1 Receptor (metabolism), RNA, Viral (blood), Receptors, Cell Surface (metabolism), Transforming Growth Factor beta1 (immunology), Transforming Growth Factor beta1 (metabolism), Tumor Necrosis Factor-alpha (metabolism), Viral Load.
MESH :
- chemical , blood : RNA, Viral.
- chemical , immunology : Antigens, CD, Interleukin-10, Transforming Growth Factor beta1.
- chemical , metabolism : Antigens, CD, Antigens, Surface, CTLA-4 Antigen, Interferon-gamma, Interleukin-10, Interleukin-2, Programmed Cell Death 1 Receptor, Receptors, Cell Surface, Transforming Growth Factor beta1, Tumor Necrosis Factor-alpha.
- chemical : Antibodies, Neutralizing.
- geographic : Germany.
- diagnosis : Hepatitis C, Chronic.
- genetics : Hepacivirus.
- immunology : CD4-Positive T-Lymphocytes, Hepacivirus, Hepatitis C, Chronic, Herpesvirus 4, Human, Orthomyxoviridae.
- virology : CD4-Positive T-Lymphocytes.
- Case-Control Studies, Cell Proliferation, Cells, Cultured, Female, Humans, Lymphocyte Activation, Male, Middle Aged, Viral Load.

Abstract

BACKGROUND & AIMS

Inhibitory receptors such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of CD4+ T cells.

METHODS

We investigated the functions of inhibitory molecules on hepatitis C virus (HCV)-, influenza-, and Epstein-Barr virus (EBV)-specific CD4+ T cells in patients with chronic infections compared with patients with resolved HCV infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using major histocompatibility complex class II tetramers. We investigated the effects of in vitro inhibition of various inhibitory pathways on proliferation and cytokine production by CD4+ T cells, and we compared these effects with those from inhibition of interleukin (IL)-10 and transforming growth factor (TGF)-β1.

RESULTS

PD-1 and CTLA-4 were up-regulated on virus-specific CD4+ T cells from patients with chronic HCV infections. PD-1 expression was lower on influenza- than on HCV-specific CD4+ T cells from subjects with chronic HCV infection, whereas CTLA-4 was expressed at similar levels, independent of their specificity. CD305 and CD200R were up-regulated in HCV resolvers. Blockade of PD-L1/2, IL-10, and TGF-β1 increased expansion of CD4+ T cells in patients with chronic HCV, whereas inhibition of IL-10 and TGF-β1 was most effective in restoring HCV-specific production of interferon gamma, IL-2, and tumor necrosis factor α.

CONCLUSIONS

We characterized expression of inhibitory molecules on HCV-, influenza-, and EBV-specific CD4+ T cells and the effects of in vitro blockade on CD4+ T-cell expansion and cytokine production. Inhibition of PD-1, IL-10, and TGF-β1 is most efficient in restoration of HCV-specific CD4+ T cells.

DOI: 10.1053/j.gastro.2011.07.004
PubMed: 21763239

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000272
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Le document en format XML

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<term>Cellules cultivées</term>
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<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND & AIMS</b>
</p>
<p>Inhibitory receptors such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of CD4+ T cells.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>We investigated the functions of inhibitory molecules on hepatitis C virus (HCV)-, influenza-, and Epstein-Barr virus (EBV)-specific CD4+ T cells in patients with chronic infections compared with patients with resolved HCV infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using major histocompatibility complex class II tetramers. We investigated the effects of in vitro inhibition of various inhibitory pathways on proliferation and cytokine production by CD4+ T cells, and we compared these effects with those from inhibition of interleukin (IL)-10 and transforming growth factor (TGF)-β1.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>PD-1 and CTLA-4 were up-regulated on virus-specific CD4+ T cells from patients with chronic HCV infections. PD-1 expression was lower on influenza- than on HCV-specific CD4+ T cells from subjects with chronic HCV infection, whereas CTLA-4 was expressed at similar levels, independent of their specificity. CD305 and CD200R were up-regulated in HCV resolvers. Blockade of PD-L1/2, IL-10, and TGF-β1 increased expansion of CD4+ T cells in patients with chronic HCV, whereas inhibition of IL-10 and TGF-β1 was most effective in restoring HCV-specific production of interferon gamma, IL-2, and tumor necrosis factor α.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b>
</p>
<p>We characterized expression of inhibitory molecules on HCV-, influenza-, and EBV-specific CD4+ T cells and the effects of in vitro blockade on CD4+ T-cell expansion and cytokine production. Inhibition of PD-1, IL-10, and TGF-β1 is most efficient in restoration of HCV-specific CD4+ T cells.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21763239</PMID>
<DateCompleted><Year>2011</Year>
<Month>11</Month>
<Day>28</Day>
</DateCompleted>
<DateRevised><Year>2011</Year>
<Month>10</Month>
<Day>04</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1528-0012</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>141</Volume>
<Issue>4</Issue>
<PubDate><Year>2011</Year>
<Month>Oct</Month>
</PubDate>
</JournalIssue>
<Title>Gastroenterology</Title>
<ISOAbbreviation>Gastroenterology</ISOAbbreviation>
</Journal>
<ArticleTitle>Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.</ArticleTitle>
<Pagination><MedlinePgn>1422-31, 1431.e1-6</MedlinePgn>
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<ELocationID EIdType="doi" ValidYN="Y">10.1053/j.gastro.2011.07.004</ELocationID>
<Abstract><AbstractText Label="BACKGROUND & AIMS" NlmCategory="OBJECTIVE">Inhibitory receptors such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of CD4+ T cells.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">We investigated the functions of inhibitory molecules on hepatitis C virus (HCV)-, influenza-, and Epstein-Barr virus (EBV)-specific CD4+ T cells in patients with chronic infections compared with patients with resolved HCV infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using major histocompatibility complex class II tetramers. We investigated the effects of in vitro inhibition of various inhibitory pathways on proliferation and cytokine production by CD4+ T cells, and we compared these effects with those from inhibition of interleukin (IL)-10 and transforming growth factor (TGF)-β1.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">PD-1 and CTLA-4 were up-regulated on virus-specific CD4+ T cells from patients with chronic HCV infections. PD-1 expression was lower on influenza- than on HCV-specific CD4+ T cells from subjects with chronic HCV infection, whereas CTLA-4 was expressed at similar levels, independent of their specificity. CD305 and CD200R were up-regulated in HCV resolvers. Blockade of PD-L1/2, IL-10, and TGF-β1 increased expansion of CD4+ T cells in patients with chronic HCV, whereas inhibition of IL-10 and TGF-β1 was most effective in restoring HCV-specific production of interferon gamma, IL-2, and tumor necrosis factor α.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">We characterized expression of inhibitory molecules on HCV-, influenza-, and EBV-specific CD4+ T cells and the effects of in vitro blockade on CD4+ T-cell expansion and cytokine production. Inhibition of PD-1, IL-10, and TGF-β1 is most efficient in restoration of HCV-specific CD4+ T cells.</AbstractText>
<CopyrightInformation>Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Raziorrouh</LastName>
<ForeName>Bijan</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Medical Department II, University Hospital of Ludwig-Maximillians-University, and Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany. bijan.raziorrouh@med.uni-muenchen.de</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ulsenheimer</LastName>
<ForeName>Axel</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Schraut</LastName>
<ForeName>Winfried</ForeName>
<Initials>W</Initials>
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<Author ValidYN="Y"><LastName>Heeg</LastName>
<ForeName>Malte</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Kurktschiev</LastName>
<ForeName>Peter</ForeName>
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<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
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<MeshHeading><DescriptorName UI="D009975" MajorTopicYN="N">Orthomyxoviridae</DescriptorName>
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<MeshHeading><DescriptorName UI="D014409" MajorTopicYN="N">Tumor Necrosis Factor-alpha</DescriptorName>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year>
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<PubMedPubDate PubStatus="revised"><Year>2011</Year>
<Month>06</Month>
<Day>27</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2011</Year>
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<name sortKey="Gruner, Norbert H" sort="Gruner, Norbert H" uniqKey="Gruner N" first="Norbert H" last="Grüner">Norbert H. Grüner</name>
<name sortKey="Haas, Jurgen" sort="Haas, Jurgen" uniqKey="Haas J" first="Jürgen" last="Haas">Jürgen Haas</name>
<name sortKey="Heeg, Malte" sort="Heeg, Malte" uniqKey="Heeg M" first="Malte" last="Heeg">Malte Heeg</name>
<name sortKey="Horster, Sophia" sort="Horster, Sophia" uniqKey="Horster S" first="Sophia" last="Horster">Sophia Horster</name>
<name sortKey="Jung, Maria Christina" sort="Jung, Maria Christina" uniqKey="Jung M" first="Maria-Christina" last="Jung">Maria-Christina Jung</name>
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<name sortKey="Neumann Haefelin, Christoph" sort="Neumann Haefelin, Christoph" uniqKey="Neumann Haefelin C" first="Christoph" last="Neumann-Haefelin">Christoph Neumann-Haefelin</name>
<name sortKey="Schraut, Winfried" sort="Schraut, Winfried" uniqKey="Schraut W" first="Winfried" last="Schraut">Winfried Schraut</name>
<name sortKey="Spannagl, Michael" sort="Spannagl, Michael" uniqKey="Spannagl M" first="Michael" last="Spannagl">Michael Spannagl</name>
<name sortKey="Thimme, Robert" sort="Thimme, Robert" uniqKey="Thimme R" first="Robert" last="Thimme">Robert Thimme</name>
<name sortKey="Ulsenheimer, Axel" sort="Ulsenheimer, Axel" uniqKey="Ulsenheimer A" first="Axel" last="Ulsenheimer">Axel Ulsenheimer</name>
<name sortKey="W Chtler, Martin" sort="W Chtler, Martin" uniqKey="W Chtler M" first="Martin" last="W Chtler">Martin W Chtler</name>
<name sortKey="Zachoval, Reinhart" sort="Zachoval, Reinhart" uniqKey="Zachoval R" first="Reinhart" last="Zachoval">Reinhart Zachoval</name>
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<country name="Allemagne"><region name="Bavière"><name sortKey="Raziorrouh, Bijan" sort="Raziorrouh, Bijan" uniqKey="Raziorrouh B" first="Bijan" last="Raziorrouh">Bijan Raziorrouh</name>
</region>
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Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.

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