Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes
Identifieur interne : 000698 ( Istex/Corpus ); précédent : 000697; suivant : 000699Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes
Auteurs : Kerry J. Laing ; Amalia S. Magaret ; Dawn E. Mueller ; Lin Zhao ; Christine Johnston ; Stephen C. De Rosa ; David M. Koelle ; Anna Wald ; Lawrence CoreySource :
- Journal of Clinical Immunology [ 0271-9142 ] ; 2010-09-01.
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Abstract
Abstract: CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.
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DOI: 10.1007/s10875-010-9441-2
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Laing</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Magaret, Amalia S" sort="Magaret, Amalia S" uniqKey="Magaret A" first="Amalia S." last="Magaret">Amalia S. Magaret</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Mueller, Dawn E" sort="Mueller, Dawn E" uniqKey="Mueller D" first="Dawn E." last="Mueller">Dawn E. Mueller</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Johnston, Christine" sort="Johnston, Christine" uniqKey="Johnston C" first="Christine" last="Johnston">Christine Johnston</name><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="De Rosa, Stephen C" sort="De Rosa, Stephen C" uniqKey="De Rosa S" first="Stephen C." last="De Rosa">Stephen C. De Rosa</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Center for AIDS Research, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Koelle, David M" sort="Koelle, David M" uniqKey="Koelle D" first="David M." last="Koelle">David M. Koelle</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Global Health, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Benaroya Research Institute, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Wald, Anna" sort="Wald, Anna" uniqKey="Wald A" first="Anna" last="Wald">Anna Wald</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation></author><author><name sortKey="Corey, Lawrence" sort="Corey, Lawrence" uniqKey="Corey L" first="Lawrence" last="Corey">Lawrence Corey</name><affiliation><mods:affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, LE-500, 98109-1024, Seattle, WA, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: lcorey@u.washington.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Clinical Immunology</title><title level="j" type="abbrev">J Clin Immunol</title><idno type="ISSN">0271-9142</idno><idno type="eISSN">1573-2592</idno><imprint><publisher>Springer US; http://www.springer-ny.com</publisher><pubPlace>Boston</pubPlace><date type="published" when="2010-09-01">2010-09-01</date><biblScope unit="volume">30</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="703">703</biblScope><biblScope unit="page" to="722">722</biblScope></imprint><idno type="ISSN">0271-9142</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0271-9142</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>HSV-2</term><term>T cells</term><term>antigens/peptides/epitopes</term><term>virus</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Kerry J. Laing</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string></affiliations></json:item><json:item><name>Amalia S. Magaret</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</json:string></affiliations></json:item><json:item><name>Dawn E. 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De Rosa</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Center for AIDS Research, University of Washington, Seattle, WA, USA</json:string></affiliations></json:item><json:item><name>David M. Koelle</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Department of Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Department of Global Health, University of Washington, Seattle, WA, USA</json:string><json:string>Benaroya Research Institute, Seattle, WA, USA</json:string></affiliations></json:item><json:item><name>Anna Wald</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Department of Epidemiology, University of Washington, Seattle, WA, USA</json:string><json:string>Department of Medicine, University of Washington, Seattle, WA, USA</json:string></affiliations></json:item><json:item><name>Lawrence Corey</name><affiliations><json:string>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</json:string><json:string>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Department of Medicine, University of Washington, Seattle, WA, USA</json:string><json:string>Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, LE-500, 98109-1024, Seattle, WA, USA</json:string><json:string>E-mail: lcorey@u.washington.edu</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>HSV-2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>T cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>antigens/peptides/epitopes</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ICS : Intracellular cytokine staining</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ORF : Open-reading frame</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CEF : CMV, EBV and flu</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MFI : Median fluorescence intensity</value></json:item></subject><articleId><json:string>9441</json:string><json:string>s10875-010-9441-2</json:string></articleId><arkIstex>ark:/67375/VQC-KWRGC17Z-B</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.</abstract><qualityIndicators><refBibsNative>false</refBibsNative><abstractWordCount>143</abstractWordCount><abstractCharCount>1010</abstractCharCount><keywordCount>8</keywordCount><score>8.716</score><pdfWordCount>10743</pdfWordCount><pdfCharCount>72969</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>20</pdfPageCount><pdfPageSize>595.276 x 790.866 pts</pdfPageSize></qualityIndicators><title>Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes</title><genre><json:string>research-article</json:string></genre><host><title>Journal of Clinical Immunology</title><language><json:string>unknown</json:string></language><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><issn><json:string>0271-9142</json:string></issn><eissn><json:string>1573-2592</json:string></eissn><journalId><json:string>10875</json:string></journalId><volume>30</volume><issue>5</issue><pages><first>703</first><last>722</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Medical Microbiology</value></json:item><json:item><value>Internal Medicine</value></json:item><json:item><value>Infectious Diseases</value></json:item><json:item><value>Immunology</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-KWRGC17Z-B</json:string></ark><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1007/s10875-010-9441-2</json:string></doi><id>2A20EB8244DE6BF056358827BB16C185EC05AD9C</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-KWRGC17Z-B/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-KWRGC17Z-B/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-KWRGC17Z-B/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">Springer US; 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Box 19024, LE-500, 98109-1024, Seattle, WA, USA</affiliation></author><idno type="istex">2A20EB8244DE6BF056358827BB16C185EC05AD9C</idno><idno type="ark">ark:/67375/VQC-KWRGC17Z-B</idno><idno type="DOI">10.1007/s10875-010-9441-2</idno><idno type="article-id">9441</idno><idno type="article-id">s10875-010-9441-2</idno></analytic><monogr><title level="j">Journal of Clinical Immunology</title><title level="j" type="abbrev">J Clin Immunol</title><idno type="pISSN">0271-9142</idno><idno type="eISSN">1573-2592</idno><idno type="journal-ID">true</idno><idno type="issue-article-count">18</idno><idno type="volume-issue-count">6</idno><imprint><publisher>Springer US; http://www.springer-ny.com</publisher><pubPlace>Boston</pubPlace><date type="published" when="2010-09-01"></date><biblScope unit="volume">30</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="703">703</biblScope><biblScope unit="page" to="722">722</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010-05-27</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>HSV-2</term></item><item><term>T cells</term></item><item><term>antigens/peptides/epitopes</term></item><item><term>virus</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>ICS</term><term>Intracellular cytokine staining</term></item><item><term>ORF</term><term>Open-reading frame</term></item><item><term>CEF</term><term>CMV, EBV and flu</term></item><item><term>MFI</term><term>Median fluorescence intensity</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Biomedicine</head><item><term>Medical Microbiology</term></item><item><term>Internal Medicine</term></item><item><term>Infectious Diseases</term></item><item><term>Immunology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-05-27">Created</change><change when="2010-09-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-KWRGC17Z-B/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus springer-journals not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType><istex:document><Publisher><PublisherInfo><PublisherName>Springer US</PublisherName><PublisherLocation>Boston</PublisherLocation><PublisherURL>http://www.springer-ny.com</PublisherURL></PublisherInfo><Journal OutputMedium="All"><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>10875</JournalID><JournalPrintISSN>0271-9142</JournalPrintISSN><JournalElectronicISSN>1573-2592</JournalElectronicISSN><JournalTitle>Journal of Clinical Immunology</JournalTitle><JournalAbbreviatedTitle>J Clin Immunol</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Biomedicine</JournalSubject><JournalSubject Type="Secondary">Medical Microbiology </JournalSubject><JournalSubject Type="Secondary">Internal Medicine</JournalSubject><JournalSubject Type="Secondary">Infectious Diseases</JournalSubject><JournalSubject Type="Secondary">Immunology</JournalSubject></JournalSubjectGroup></JournalInfo><Volume OutputMedium="All"><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>30</VolumeIDStart><VolumeIDEnd>30</VolumeIDEnd><VolumeIssueCount>6</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular" OutputMedium="All"><IssueInfo IssueType="Regular" TocLevels="0"><IssueIDStart>5</IssueIDStart><IssueIDEnd>5</IssueIDEnd><IssueTitle Language="En">MINI REVIEWS: INFLAMMASOME AND INFLAMMATION (PART 2)</IssueTitle><IssueArticleCount>18</IssueArticleCount><IssueHistory><OnlineDate><Year>2010</Year><Month>9</Month><Day>9</Day></OnlineDate><PrintDate><Year>2010</Year><Month>9</Month><Day>8</Day></PrintDate><CoverDate><Year>2010</Year><Month>9</Month></CoverDate><PricelistYear>2010</PricelistYear></IssueHistory><IssueCopyright><CopyrightHolderName>Springer Science+Business Media, LLC</CopyrightHolderName><CopyrightYear>2010</CopyrightYear></IssueCopyright></IssueInfo><Article ID="s10875-010-9441-2" OutputMedium="All"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="Yes" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>9441</ArticleID><ArticleDOI>10.1007/s10875-010-9441-2</ArticleDOI><ArticleSequenceNumber>12</ArticleSequenceNumber><ArticleTitle Language="En">Diversity in CD8<Superscript>+</Superscript> T Cell Function and Epitope Breadth Among Persons with Genital Herpes</ArticleTitle><ArticleFirstPage>703</ArticleFirstPage><ArticleLastPage>722</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2010</Year><Month>6</Month><Day>16</Day></RegistrationDate><Received><Year>2010</Year><Month>5</Month><Day>27</Day></Received><Accepted><Year>2010</Year><Month>6</Month><Day>15</Day></Accepted><OnlineDate><Year>2010</Year><Month>7</Month><Day>16</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer Science+Business Media, LLC</CopyrightHolderName><CopyrightYear>2010</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Kerry</GivenName><GivenName>J.</GivenName><FamilyName>Laing</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff3"><AuthorName DisplayOrder="Western"><GivenName>Amalia</GivenName><GivenName>S.</GivenName><FamilyName>Magaret</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Dawn</GivenName><GivenName>E.</GivenName><FamilyName>Mueller</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Lin</GivenName><FamilyName>Zhao</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Christine</GivenName><FamilyName>Johnston</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2 Aff3 Aff6"><AuthorName DisplayOrder="Western"><GivenName>Stephen</GivenName><GivenName>C.</GivenName><Particle>De</Particle><FamilyName>Rosa</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff3 Aff5 Aff7 Aff8"><AuthorName DisplayOrder="Western"><GivenName>David</GivenName><GivenName>M.</GivenName><FamilyName>Koelle</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff3 Aff4 Aff5"><AuthorName DisplayOrder="Western"><GivenName>Anna</GivenName><FamilyName>Wald</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff3 Aff5 Aff9" CorrespondingAffiliationID="Aff9"><AuthorName DisplayOrder="Western"><GivenName>Lawrence</GivenName><FamilyName>Corey</FamilyName></AuthorName><Contact><Email>lcorey@u.washington.edu</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Vaccine and Infectious Disease Division</OrgDivision><OrgName>Fred Hutchinson Cancer Research Center</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>HIV Vaccine Trials Network</OrgDivision><OrgName>Fred Hutchinson Cancer Research Center</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff3"><OrgDivision>Department of Laboratory Medicine</OrgDivision><OrgName>University of Washington</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff4"><OrgDivision>Department of Epidemiology</OrgDivision><OrgName>University of Washington</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff5"><OrgDivision>Department of Medicine</OrgDivision><OrgName>University of Washington</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff6"><OrgDivision>Center for AIDS Research</OrgDivision><OrgName>University of Washington</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff7"><OrgDivision>Department of Global Health</OrgDivision><OrgName>University of Washington</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff8"><OrgName>Benaroya Research Institute</OrgName><OrgAddress><City>Seattle</City><State>WA</State><Country Code="US">USA</Country></OrgAddress></Affiliation><Affiliation ID="Aff9"><OrgName>Fred Hutchinson Cancer Research Center</OrgName><OrgAddress><Street>1100 Fairview Avenue N</Street><Postbox>P.O. Box 19024, LE-500</Postbox><City>Seattle</City><State>WA</State><Postcode>98109-1024</Postcode><Country Code="US">USA</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>CD8<Superscript>+</Superscript> T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8<Superscript>+</Superscript> T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8<Superscript>+</Superscript> T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8<Superscript>+</Superscript> T cell epitopes. CD8<Superscript>+</Superscript> T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>HSV-2</Keyword><Keyword>T cells</Keyword><Keyword>antigens/peptides/epitopes</Keyword><Keyword>virus</Keyword></KeywordGroup><AbbreviationGroup><Heading>Abbreviations</Heading><DefinitionList><DefinitionListEntry><Term>ICS</Term><Description><Para>Intracellular cytokine staining</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>ORF</Term><Description><Para>Open-reading frame</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>CEF</Term><Description><Para>CMV, EBV and flu</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>MFI</Term><Description><Para>Median fluorescence intensity</Para></Description></DefinitionListEntry></DefinitionList></AbbreviationGroup><ArticleNote Type="ESMHint"><Heading>Electronic supplementary material</Heading><SimplePara>The online version of this article (doi:<ExternalRef><RefSource>10.1007/s10875-010-9441-2</RefSource><RefTarget Address="10.1007/s10875-010-9441-2" TargetType="DOI"></RefTarget></ExternalRef>) contains supplementary material, which is available to authorized users.</SimplePara></ArticleNote></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes</title></titleInfo><name type="personal"><namePart type="given">Kerry</namePart><namePart type="given">J.</namePart><namePart type="family">Laing</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Amalia</namePart><namePart type="given">S.</namePart><namePart type="family">Magaret</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dawn</namePart><namePart type="given">E.</namePart><namePart type="family">Mueller</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lin</namePart><namePart type="family">Zhao</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Johnston</namePart><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen</namePart><namePart type="given">C.</namePart><namePart type="family">De Rosa</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Center for AIDS Research, University of Washington, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="given">M.</namePart><namePart type="family">Koelle</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Department of Global Health, University of Washington, Seattle, WA, USA</affiliation><affiliation>Benaroya Research Institute, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anna</namePart><namePart type="family">Wald</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Department of Epidemiology, University of Washington, Seattle, WA, USA</affiliation><affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Lawrence</namePart><namePart type="family">Corey</namePart><affiliation>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA</affiliation><affiliation>Department of Laboratory Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Department of Medicine, University of Washington, Seattle, WA, USA</affiliation><affiliation>Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, LE-500, 98109-1024, Seattle, WA, USA</affiliation><affiliation>E-mail: lcorey@u.washington.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer US; http://www.springer-ny.com</publisher><place><placeTerm type="text">Boston</placeTerm></place><dateCreated encoding="w3cdtf">2010-05-27</dateCreated><dateIssued encoding="w3cdtf">2010-09-01</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: CD8+ T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8+ T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8+ T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8+ T cell epitopes. CD8+ T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.</abstract><subject lang="en"><genre>Keywords</genre><topic>HSV-2</topic><topic>T cells</topic><topic>antigens/peptides/epitopes</topic><topic>virus</topic></subject><subject><genre>Abbreviations</genre><topic>ICS : Intracellular cytokine staining</topic><topic>ORF : Open-reading frame</topic><topic>CEF : CMV, EBV and flu</topic><topic>MFI : Median fluorescence intensity</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Clinical Immunology</title></titleInfo><titleInfo type="abbreviated"><title>J Clin Immunol</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2010-09-09</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><subject><genre>Biomedicine</genre><topic>Medical Microbiology</topic><topic>Internal Medicine</topic><topic>Infectious Diseases</topic><topic>Immunology</topic></subject><identifier type="ISSN">0271-9142</identifier><identifier type="eISSN">1573-2592</identifier><identifier type="JournalID">10875</identifier><identifier type="IssueArticleCount">18</identifier><identifier type="VolumeIssueCount">6</identifier><part><date>2010</date><detail type="issue"><title>MINI REVIEWS: INFLAMMASOME AND INFLAMMATION (PART 2)</title></detail><detail type="volume"><number>30</number><caption>vol.</caption></detail><detail type="issue"><number>5</number><caption>no.</caption></detail><extent unit="pages"><start>703</start><end>722</end></extent></part><recordInfo><recordOrigin>Springer Science+Business Media, LLC, 2010</recordOrigin></recordInfo></relatedItem><identifier type="istex">2A20EB8244DE6BF056358827BB16C185EC05AD9C</identifier><identifier type="ark">ark:/67375/VQC-KWRGC17Z-B</identifier><identifier type="DOI">10.1007/s10875-010-9441-2</identifier><identifier type="ArticleID">9441</identifier><identifier type="ArticleID">s10875-010-9441-2</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media, LLC, 2010</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer Science+Business Media, LLC, 2010</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-KWRGC17Z-B/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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