Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
Identifieur interne : 003A36 ( Ncbi/Merge ); précédent : 003A35; suivant : 003A37Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
Auteurs : E. Keoshkerian [Australie] ; M. Hunter [Australie] ; B. Cameron [Australie] ; N. Nguyen [Australie] ; P. Sugden [Australie] ; R. Bull [Australie] ; A. Zekry [Australie] ; L. Maher [Australie] ; N. Seddiki [France] ; J. Zaunders [Australie] ; A. Kelleher [Australie] ; A R Lloyd [Australie]Source :
- Journal of viral hepatitis [ 1365-2893 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte, Cytokines (sécrétion), Femelle, Hepacivirus (immunologie), Humains, Hépatite C (immunologie), Lymphocytes T CD4+ (immunologie), Lymphocytes T régulateurs (immunologie), Mâle, Résultat thérapeutique, Sous-populations de lymphocytes T (immunologie), Études longitudinales, Études transversales.
- MESH :
- immunologie : Hepacivirus, Hépatite C, Lymphocytes T CD4+, Lymphocytes T régulateurs, Sous-populations de lymphocytes T.
- sécrétion : Cytokines.
- Adulte, Femelle, Humains, Mâle, Résultat thérapeutique, Études longitudinales, Études transversales.
English descriptors
- KwdEn :
- MESH :
- chemical , secretion : Cytokines.
- immunology : CD4-Positive T-Lymphocytes, Hepacivirus, Hepatitis C, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory.
- Adult, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Treatment Outcome.
Abstract
Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.
DOI: 10.1111/jvh.12576
PubMed: 27558465
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pubmed:27558465Le document en format XML
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<front><div type="abstract" xml:lang="en">Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.</div>
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<Abstract><AbstractText>Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25(high) CD134+CD39-) and T-regulatory (CD4+CD25(high) CD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.</AbstractText>
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<ForeName>N</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sugden</LastName>
<ForeName>P</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bull</LastName>
<ForeName>R</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, Kirby Institute (Viral Immunology Systems Program, VISP) and School of Medical Sciences (SOMS), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zekry</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, St George and Sutherland Clinical School, Sydney, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Maher</LastName>
<ForeName>L</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, Kirby Institute (Viral Hepatitis Epidemiology and Prevention Program VHEPP), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Seddiki</LastName>
<ForeName>N</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>The Vaccine Research Institute (VRI), INSERM, Créteil, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zaunders</LastName>
<ForeName>J</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, Kirby Institute (Immunovirology and Pathogenesis Program, IVPP), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kelleher</LastName>
<ForeName>A</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, Kirby Institute (Immunovirology and Pathogenesis Program, IVPP), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lloyd</LastName>
<ForeName>A R</ForeName>
<Initials>AR</Initials>
<AffiliationInfo><Affiliation>UNSW Australia, Kirby Institute (Viral Immunology Systems Program, VISP) and School of Medical Sciences (SOMS), Kensington, NSW, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>HITS-p and HITS-c investigators</CollectiveName>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>08</Month>
<Day>25</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>J Viral Hepat</MedlineTA>
<NlmUniqueID>9435672</NlmUniqueID>
<ISSNLinking>1352-0504</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D016207">Cytokines</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003430" MajorTopicYN="N">Cross-Sectional Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName>
<QualifierName UI="Q000557" MajorTopicYN="N">secretion</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016174" MajorTopicYN="N">Hepacivirus</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006526" MajorTopicYN="N">Hepatitis C</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008137" MajorTopicYN="N">Longitudinal Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016176" MajorTopicYN="N">T-Lymphocyte Subsets</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050378" MajorTopicYN="N">T-Lymphocytes, Regulatory</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">T effectors</Keyword>
<Keyword MajorTopicYN="N">T regulatory cells</Keyword>
<Keyword MajorTopicYN="N">acute hepatitis C</Keyword>
<Keyword MajorTopicYN="N">antigen-specific CD4 T cells</Keyword>
<Keyword MajorTopicYN="N">cytokines</Keyword>
</KeywordList>
<InvestigatorList><Investigator ValidYN="Y"><LastName>Dolan</LastName>
<ForeName>Kate</ForeName>
<Initials>K</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Haber</LastName>
<ForeName>Paul</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Rawlinson</LastName>
<ForeName>William</ForeName>
<Initials>W</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Treloar</LastName>
<ForeName>Carla</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Dore</LastName>
<ForeName>Greg</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Luciani</LastName>
<ForeName>Fabio</ForeName>
<Initials>F</Initials>
</Investigator>
</InvestigatorList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>02</Month>
<Day>23</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>06</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>8</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>10</Month>
<Day>31</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>8</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">27558465</ArticleId>
<ArticleId IdType="doi">10.1111/jvh.12576</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Australie</li>
<li>France</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Créteil</li>
</settlement>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Keoshkerian, E" sort="Keoshkerian, E" uniqKey="Keoshkerian E" first="E" last="Keoshkerian">E. Keoshkerian</name>
</noRegion>
<name sortKey="Bull, R" sort="Bull, R" uniqKey="Bull R" first="R" last="Bull">R. Bull</name>
<name sortKey="Cameron, B" sort="Cameron, B" uniqKey="Cameron B" first="B" last="Cameron">B. Cameron</name>
<name sortKey="Hunter, M" sort="Hunter, M" uniqKey="Hunter M" first="M" last="Hunter">M. Hunter</name>
<name sortKey="Kelleher, A" sort="Kelleher, A" uniqKey="Kelleher A" first="A" last="Kelleher">A. Kelleher</name>
<name sortKey="Lloyd, A R" sort="Lloyd, A R" uniqKey="Lloyd A" first="A R" last="Lloyd">A R Lloyd</name>
<name sortKey="Maher, L" sort="Maher, L" uniqKey="Maher L" first="L" last="Maher">L. Maher</name>
<name sortKey="Nguyen, N" sort="Nguyen, N" uniqKey="Nguyen N" first="N" last="Nguyen">N. Nguyen</name>
<name sortKey="Sugden, P" sort="Sugden, P" uniqKey="Sugden P" first="P" last="Sugden">P. Sugden</name>
<name sortKey="Zaunders, J" sort="Zaunders, J" uniqKey="Zaunders J" first="J" last="Zaunders">J. Zaunders</name>
<name sortKey="Zekry, A" sort="Zekry, A" uniqKey="Zekry A" first="A" last="Zekry">A. Zekry</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Seddiki, N" sort="Seddiki, N" uniqKey="Seddiki N" first="N" last="Seddiki">N. Seddiki</name>
</region>
</country>
</tree>
</affiliations>
</record>
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