Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.
Identifieur interne : 000295 ( Main/Exploration ); précédent : 000294; suivant : 000296Inhibitory 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. GrünerSource :
- Gastroenterology [ 1528-0012 ] ; 2011.
Descripteurs français
- KwdFr :
- ARN viral (sang), Activation des lymphocytes (MeSH), Adulte d'âge moyen (MeSH), Allemagne (MeSH), Anticorps neutralisants (MeSH), Antigène CTLA-4 (métabolisme), Antigènes CD (immunologie), Antigènes CD (métabolisme), Antigènes de surface (métabolisme), Cellules cultivées (MeSH), Charge virale (MeSH), Facteur de croissance transformant bêta-1 (immunologie), Facteur de croissance transformant bêta-1 (métabolisme), Facteur de nécrose tumorale alpha (métabolisme), Femelle (MeSH), Hepacivirus (génétique), Hepacivirus (immunologie), Herpèsvirus humain de type 4 (immunologie), Humains (MeSH), Hépatite C chronique (diagnostic), Hépatite C chronique (immunologie), Interféron gamma (métabolisme), Interleukine-10 (immunologie), Interleukine-10 (métabolisme), Interleukine-2 (métabolisme), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (virologie), Mâle (MeSH), Orthomyxoviridae (immunologie), Prolifération cellulaire (MeSH), Récepteur-1 de mort cellulaire programmée (métabolisme), Récepteurs de surface cellulaire (métabolisme), Études cas-témoins (MeSH).
- MESH :
- diagnostic : Hépatite C chronique.
- génétique : Hepacivirus.
- immunologie : Antigènes CD, Facteur de croissance transformant bêta-1, Hepacivirus, Herpèsvirus humain de type 4, Hépatite C chronique, Interleukine-10, Lymphocytes T CD4+, Orthomyxoviridae.
- métabolisme : Antigène CTLA-4, Antigènes CD, Antigènes de surface, Facteur de croissance transformant bêta-1, Facteur de nécrose tumorale alpha, Interféron gamma, Interleukine-10, Interleukine-2, Récepteur-1 de mort cellulaire programmée, Récepteurs de surface cellulaire.
- sang : ARN viral.
- virologie : Lymphocytes T CD4+.
- Activation des lymphocytes, Adulte d'âge moyen, Allemagne, Anticorps neutralisants, Cellules cultivées, Charge virale, Femelle, Humains, Mâle, Prolifération cellulaire, Études cas-témoins.
- Wicri :
- geographic : Allemagne.
English descriptors
- KwdEn :
- Antibodies, Neutralizing (MeSH), 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 (MeSH), Cell Proliferation (MeSH), Cells, Cultured (MeSH), Female (MeSH), Germany (MeSH), Hepacivirus (genetics), Hepacivirus (immunology), Hepatitis C, Chronic (diagnosis), Hepatitis C, Chronic (immunology), Herpesvirus 4, Human (immunology), Humans (MeSH), Interferon-gamma (metabolism), Interleukin-10 (immunology), Interleukin-10 (metabolism), Interleukin-2 (metabolism), Lymphocyte Activation (MeSH), Male (MeSH), Middle Aged (MeSH), 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).
- 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...)
Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Neutralizing (MeSH)</term>
<term>Antigens, CD (immunology)</term>
<term>Antigens, CD (metabolism)</term>
<term>Antigens, Surface (metabolism)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>CTLA-4 Antigen (metabolism)</term>
<term>Case-Control Studies (MeSH)</term>
<term>Cell Proliferation (MeSH)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Female (MeSH)</term>
<term>Germany (MeSH)</term>
<term>Hepacivirus (genetics)</term>
<term>Hepacivirus (immunology)</term>
<term>Hepatitis C, Chronic (diagnosis)</term>
<term>Hepatitis C, Chronic (immunology)</term>
<term>Herpesvirus 4, Human (immunology)</term>
<term>Humans (MeSH)</term>
<term>Interferon-gamma (metabolism)</term>
<term>Interleukin-10 (immunology)</term>
<term>Interleukin-10 (metabolism)</term>
<term>Interleukin-2 (metabolism)</term>
<term>Lymphocyte Activation (MeSH)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Orthomyxoviridae (immunology)</term>
<term>Programmed Cell Death 1 Receptor (metabolism)</term>
<term>RNA, Viral (blood)</term>
<term>Receptors, Cell Surface (metabolism)</term>
<term>Transforming Growth Factor beta1 (immunology)</term>
<term>Transforming Growth Factor beta1 (metabolism)</term>
<term>Tumor Necrosis Factor-alpha (metabolism)</term>
<term>Viral Load (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (sang)</term>
<term>Activation des lymphocytes (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Allemagne (MeSH)</term>
<term>Anticorps neutralisants (MeSH)</term>
<term>Antigène CTLA-4 (métabolisme)</term>
<term>Antigènes CD (immunologie)</term>
<term>Antigènes CD (métabolisme)</term>
<term>Antigènes de surface (métabolisme)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Charge virale (MeSH)</term>
<term>Facteur de croissance transformant bêta-1 (immunologie)</term>
<term>Facteur de croissance transformant bêta-1 (métabolisme)</term>
<term>Facteur de nécrose tumorale alpha (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Hepacivirus (génétique)</term>
<term>Hepacivirus (immunologie)</term>
<term>Herpèsvirus humain de type 4 (immunologie)</term>
<term>Humains (MeSH)</term>
<term>Hépatite C chronique (diagnostic)</term>
<term>Hépatite C chronique (immunologie)</term>
<term>Interféron gamma (métabolisme)</term>
<term>Interleukine-10 (immunologie)</term>
<term>Interleukine-10 (métabolisme)</term>
<term>Interleukine-2 (métabolisme)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (virologie)</term>
<term>Mâle (MeSH)</term>
<term>Orthomyxoviridae (immunologie)</term>
<term>Prolifération cellulaire (MeSH)</term>
<term>Récepteur-1 de mort cellulaire programmée (métabolisme)</term>
<term>Récepteurs de surface cellulaire (métabolisme)</term>
<term>Études cas-témoins (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>RNA, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, CD</term>
<term>Interleukin-10</term>
<term>Transforming Growth Factor beta1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD</term>
<term>Antigens, Surface</term>
<term>CTLA-4 Antigen</term>
<term>Interferon-gamma</term>
<term>Interleukin-10</term>
<term>Interleukin-2</term>
<term>Programmed Cell Death 1 Receptor</term>
<term>Receptors, Cell Surface</term>
<term>Transforming Growth Factor beta1</term>
<term>Tumor Necrosis Factor-alpha</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antibodies, Neutralizing</term>
</keywords>
<keywords scheme="MESH" type="geographic" xml:lang="en"><term>Germany</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Hepatitis C, Chronic</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Hépatite C chronique</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hepacivirus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Hepacivirus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes CD</term>
<term>Facteur de croissance transformant bêta-1</term>
<term>Hepacivirus</term>
<term>Herpèsvirus humain de type 4</term>
<term>Hépatite C chronique</term>
<term>Interleukine-10</term>
<term>Lymphocytes T CD4+</term>
<term>Orthomyxoviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Hepacivirus</term>
<term>Hepatitis C, Chronic</term>
<term>Herpesvirus 4, Human</term>
<term>Orthomyxoviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Antigènes CD</term>
<term>Antigènes de surface</term>
<term>Facteur de croissance transformant bêta-1</term>
<term>Facteur de nécrose tumorale alpha</term>
<term>Interféron gamma</term>
<term>Interleukine-10</term>
<term>Interleukine-2</term>
<term>Récepteur-1 de mort cellulaire programmée</term>
<term>Récepteurs de surface cellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ARN viral</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lymphocytes T CD4+</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Female</term>
<term>Humans</term>
<term>Lymphocyte Activation</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term>
<term>Adulte d'âge moyen</term>
<term>Allemagne</term>
<term>Anticorps neutralisants</term>
<term>Cellules cultivées</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Prolifération cellulaire</term>
<term>Études cas-témoins</term>
</keywords>
<keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Allemagne</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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>
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<Day>28</Day>
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<Month>10</Month>
<Day>04</Day>
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<Month>Oct</Month>
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<Title>Gastroenterology</Title>
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<ArticleTitle>Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection.</ArticleTitle>
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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>
</Author>
<Author ValidYN="Y"><LastName>Heeg</LastName>
<ForeName>Malte</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Kurktschiev</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
</Author>
<Author ValidYN="Y"><LastName>Zachoval</LastName>
<ForeName>Reinhart</ForeName>
<Initials>R</Initials>
</Author>
<Author ValidYN="Y"><LastName>Jung</LastName>
<ForeName>Maria-Christina</ForeName>
<Initials>MC</Initials>
</Author>
<Author ValidYN="Y"><LastName>Thimme</LastName>
<ForeName>Robert</ForeName>
<Initials>R</Initials>
</Author>
<Author ValidYN="Y"><LastName>Neumann-Haefelin</LastName>
<ForeName>Christoph</ForeName>
<Initials>C</Initials>
</Author>
<Author ValidYN="Y"><LastName>Horster</LastName>
<ForeName>Sophia</ForeName>
<Initials>S</Initials>
</Author>
<Author ValidYN="Y"><LastName>Wächtler</LastName>
<ForeName>Martin</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Spannagl</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Haas</LastName>
<ForeName>Jürgen</ForeName>
<Initials>J</Initials>
</Author>
<Author ValidYN="Y"><LastName>Diepolder</LastName>
<ForeName>Helmut M</ForeName>
<Initials>HM</Initials>
</Author>
<Author ValidYN="Y"><LastName>Grüner</LastName>
<ForeName>Norbert H</ForeName>
<Initials>NH</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2011</Year>
<Month>07</Month>
<Day>18</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Gastroenterology</MedlineTA>
<NlmUniqueID>0374630</NlmUniqueID>
<ISSNLinking>0016-5085</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000954">Antigens, Surface</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C477337">CD200R1 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D060908">CTLA-4 Antigen</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C508609">IL10 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C508594">IL2 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007376">Interleukin-2</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C105992">PDCD1 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D061026">Programmed Cell Death 1 Receptor</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D012367">RNA, Viral</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011956">Receptors, Cell Surface</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C508960">TGFB1 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D053773">Transforming Growth Factor beta1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014409">Tumor Necrosis Factor-alpha</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>130068-27-8</RegistryNumber>
<NameOfSubstance UI="D016753">Interleukin-10</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>82115-62-6</RegistryNumber>
<NameOfSubstance UI="D007371">Interferon-gamma</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000954" MajorTopicYN="N">Antigens, Surface</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D060908" MajorTopicYN="N">CTLA-4 Antigen</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016022" MajorTopicYN="N">Case-Control Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="Y">Cell Proliferation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005858" MajorTopicYN="N" Type="Geographic">Germany</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016174" MajorTopicYN="N">Hepacivirus</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019698" MajorTopicYN="N">Hepatitis C, Chronic</DescriptorName>
<QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004854" MajorTopicYN="N">Herpesvirus 4, Human</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007371" MajorTopicYN="N">Interferon-gamma</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016753" MajorTopicYN="N">Interleukin-10</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007376" MajorTopicYN="N">Interleukin-2</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="Y">Lymphocyte Activation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009975" MajorTopicYN="N">Orthomyxoviridae</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061026" MajorTopicYN="N">Programmed Cell Death 1 Receptor</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012367" MajorTopicYN="N">RNA, Viral</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011956" MajorTopicYN="N">Receptors, Cell Surface</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053773" MajorTopicYN="N">Transforming Growth Factor beta1</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014409" MajorTopicYN="N">Tumor Necrosis Factor-alpha</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year>
<Month>09</Month>
<Day>30</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2011</Year>
<Month>06</Month>
<Day>27</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2011</Year>
<Month>07</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2011</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2011</Year>
<Month>7</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2011</Year>
<Month>12</Month>
<Day>13</Day>
<Hour>0</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">21763239</ArticleId>
<ArticleId IdType="pii">S0016-5085(11)00942-5</ArticleId>
<ArticleId IdType="doi">10.1053/j.gastro.2011.07.004</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Bavière</li>
<li>District de Haute-Bavière</li>
</region>
<settlement><li>Munich</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Diepolder, Helmut M" sort="Diepolder, Helmut M" uniqKey="Diepolder H" first="Helmut M" last="Diepolder">Helmut M. Diepolder</name>
<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>
<name sortKey="Kurktschiev, Peter" sort="Kurktschiev, Peter" uniqKey="Kurktschiev P" first="Peter" last="Kurktschiev">Peter Kurktschiev</name>
<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>
</noCountry>
<country name="Allemagne"><region name="Bavière"><name sortKey="Raziorrouh, Bijan" sort="Raziorrouh, Bijan" uniqKey="Raziorrouh B" first="Bijan" last="Raziorrouh">Bijan Raziorrouh</name>
</region>
</country>
</tree>
</affiliations>
</record>
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