Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus.
Identifieur interne : 002235 ( Main/Curation ); précédent : 002234; suivant : 002236Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus.
Auteurs : Anthony Brown [Royaume-Uni] ; John S. Halliday [Royaume-Uni] ; Leo Swadling [Royaume-Uni] ; Richie G. Madden [Royaume-Uni] ; Richard Bendall [Royaume-Uni] ; Jeremy G. Hunter [Royaume-Uni] ; James Maggs [Royaume-Uni] ; Peter Simmonds [Royaume-Uni] ; Donald B. Smith [Royaume-Uni] ; Louisa Vine [Royaume-Uni] ; Cara Mclaughlin [Royaume-Uni] ; Jane Collier [Royaume-Uni] ; David Bonsall [Royaume-Uni] ; Katie Jeffery [Royaume-Uni] ; Susanna Dunachie [Royaume-Uni] ; Paul Klenerman [Royaume-Uni] ; Jacques Izopet [France] ; Nassim Kamar [France] ; Harry R. Dalton [Royaume-Uni] ; Eleanor Barnes [Royaume-Uni]Source :
- Hepatology (Baltimore, Md.) [ 1527-3350 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Facteurs temps, Femelle, Humains, Hépatite E (diagnostic), Hépatite E (immunologie), Hépatite E (sang), Hépatite E (virologie), Interféron gamma (sang), Jeune adulte, Lymphocytes T (immunologie), Lymphocytes T (virologie), Mâle, Spécificité antigénique des récepteurs des lymphocytes T, Sujet âgé, Sujet âgé de 80 ans ou plus, Virus de l'hépatite E (immunologie).
- MESH :
- diagnostic : Hépatite E.
- immunologie : Hépatite E, Lymphocytes T, Virus de l'hépatite E.
- sang : Hépatite E, Interféron gamma.
- virologie : Hépatite E, Lymphocytes T.
- Adulte, Adulte d'âge moyen, Facteurs temps, Femelle, Humains, Jeune adulte, Mâle, Spécificité antigénique des récepteurs des lymphocytes T, Sujet âgé, Sujet âgé de 80 ans ou plus.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Female, Hepatitis E (blood), Hepatitis E (diagnosis), Hepatitis E (immunology), Hepatitis E (virology), Hepatitis E virus (immunology), Humans, Interferon-gamma (blood), Male, Middle Aged, T-Cell Antigen Receptor Specificity, T-Lymphocytes (immunology), T-Lymphocytes (virology), Time Factors, Young Adult.
- MESH :
- chemical , blood : Interferon-gamma.
- blood : Hepatitis E.
- diagnosis : Hepatitis E.
- immunology : Hepatitis E, Hepatitis E virus, T-Lymphocytes.
- virology : Hepatitis E, T-Lymphocytes.
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, T-Cell Antigen Receptor Specificity, Time Factors, Young Adult.
Abstract
The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4(+) /CD8(+) T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/10(6) peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8(+) T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8(+) responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4(+) and CD8(+) T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL.
DOI: 10.1002/hep.28819
PubMed: 27631819
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sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Izopet, Jacques" sort="Izopet, Jacques" uniqKey="Izopet J" first="Jacques" last="Izopet">Jacques Izopet</name><affiliation wicri:level="3"><nlm:affiliation>The Rangueil Hospital, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>The Rangueil Hospital, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Kamar, Nassim" sort="Kamar, Nassim" uniqKey="Kamar N" first="Nassim" last="Kamar">Nassim Kamar</name><affiliation wicri:level="3"><nlm:affiliation>The Rangueil Hospital, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>The Rangueil Hospital, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Dalton, Harry R" sort="Dalton, Harry R" uniqKey="Dalton H" first="Harry R" last="Dalton">Harry R. Dalton</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Barnes, Eleanor" sort="Barnes, Eleanor" uniqKey="Barnes E" first="Eleanor" last="Barnes">Eleanor Barnes</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27631819</idno><idno type="pmid">27631819</idno><idno type="doi">10.1002/hep.28819</idno><idno type="wicri:Area/PubMed/Corpus">001442</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001442</idno><idno type="wicri:Area/PubMed/Curation">001420</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001420</idno><idno type="wicri:Area/PubMed/Checkpoint">001420</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001420</idno><idno type="wicri:Area/Ncbi/Merge">003B45</idno><idno type="wicri:Area/Ncbi/Curation">003B45</idno><idno type="wicri:Area/Ncbi/Checkpoint">003B45</idno><idno type="wicri:Area/Main/Merge">002234</idno><idno type="wicri:Area/Main/Curation">002235</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus.</title><author><name sortKey="Brown, Anthony" sort="Brown, Anthony" uniqKey="Brown A" first="Anthony" last="Brown">Anthony Brown</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Halliday, John S" sort="Halliday, John S" uniqKey="Halliday J" first="John S" last="Halliday">John S. Halliday</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Swadling, Leo" sort="Swadling, Leo" uniqKey="Swadling L" first="Leo" last="Swadling">Leo Swadling</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Madden, Richie G" sort="Madden, Richie G" uniqKey="Madden R" first="Richie G" last="Madden">Richie G. Madden</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Bendall, Richard" sort="Bendall, Richard" uniqKey="Bendall R" first="Richard" last="Bendall">Richard Bendall</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Hunter, Jeremy G" sort="Hunter, Jeremy G" uniqKey="Hunter J" first="Jeremy G" last="Hunter">Jeremy G. Hunter</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Maggs, James" sort="Maggs, James" uniqKey="Maggs J" first="James" last="Maggs">James Maggs</name><affiliation wicri:level="3"><nlm:affiliation>Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford University Hospitals NHS Foundation Trust, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Simmonds, Peter" sort="Simmonds, Peter" uniqKey="Simmonds P" first="Peter" last="Simmonds">Peter Simmonds</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Smith, Donald B" sort="Smith, Donald B" uniqKey="Smith D" first="Donald B" last="Smith">Donald B. Smith</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Immunity, Infection and Evolution, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Immunity, Infection and Evolution, University of Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Vine, Louisa" sort="Vine, Louisa" uniqKey="Vine L" first="Louisa" last="Vine">Louisa Vine</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Mclaughlin, Cara" sort="Mclaughlin, Cara" uniqKey="Mclaughlin C" first="Cara" last="Mclaughlin">Cara Mclaughlin</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Collier, Jane" sort="Collier, Jane" uniqKey="Collier J" first="Jane" last="Collier">Jane Collier</name><affiliation wicri:level="3"><nlm:affiliation>Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford University Hospitals NHS Foundation Trust, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Bonsall, David" sort="Bonsall, David" uniqKey="Bonsall D" first="David" last="Bonsall">David Bonsall</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Jeffery, Katie" sort="Jeffery, Katie" uniqKey="Jeffery K" first="Katie" last="Jeffery">Katie Jeffery</name><affiliation wicri:level="3"><nlm:affiliation>Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Oxford University Hospitals NHS Foundation Trust, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Dunachie, Susanna" sort="Dunachie, Susanna" uniqKey="Dunachie S" first="Susanna" last="Dunachie">Susanna Dunachie</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Izopet, Jacques" sort="Izopet, Jacques" uniqKey="Izopet J" first="Jacques" last="Izopet">Jacques Izopet</name><affiliation wicri:level="3"><nlm:affiliation>The Rangueil Hospital, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>The Rangueil Hospital, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Kamar, Nassim" sort="Kamar, Nassim" uniqKey="Kamar N" first="Nassim" last="Kamar">Nassim Kamar</name><affiliation wicri:level="3"><nlm:affiliation>The Rangueil Hospital, Toulouse, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>The Rangueil Hospital, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Dalton, Harry R" sort="Dalton, Harry R" uniqKey="Dalton H" first="Harry R" last="Dalton">Harry R. Dalton</name><affiliation wicri:level="1"><nlm:affiliation>The Royal Cornwall Hospital, Truro, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Royal Cornwall Hospital, Truro</wicri:regionArea><wicri:noRegion>Truro</wicri:noRegion></affiliation></author><author><name sortKey="Barnes, Eleanor" sort="Barnes, Eleanor" uniqKey="Barnes E" first="Eleanor" last="Barnes">Eleanor Barnes</name><affiliation wicri:level="4"><nlm:affiliation>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Peter Medawar Building for Pathogen Research, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></analytic><series><title level="j">Hepatology (Baltimore, Md.)</title><idno type="eISSN">1527-3350</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Female</term><term>Hepatitis E (blood)</term><term>Hepatitis E (diagnosis)</term><term>Hepatitis E (immunology)</term><term>Hepatitis E (virology)</term><term>Hepatitis E virus (immunology)</term><term>Humans</term><term>Interferon-gamma (blood)</term><term>Male</term><term>Middle Aged</term><term>T-Cell Antigen Receptor Specificity</term><term>T-Lymphocytes (immunology)</term><term>T-Lymphocytes (virology)</term><term>Time Factors</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Facteurs temps</term><term>Femelle</term><term>Humains</term><term>Hépatite E (diagnostic)</term><term>Hépatite E (immunologie)</term><term>Hépatite E (sang)</term><term>Hépatite E (virologie)</term><term>Interféron gamma (sang)</term><term>Jeune adulte</term><term>Lymphocytes T (immunologie)</term><term>Lymphocytes T (virologie)</term><term>Mâle</term><term>Spécificité antigénique des récepteurs des lymphocytes T</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Virus de l'hépatite E (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Interferon-gamma</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Hepatitis E</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Hepatitis E</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Hépatite E</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Hépatite E</term><term>Lymphocytes T</term><term>Virus de l'hépatite E</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Hepatitis E</term><term>Hepatitis E virus</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Hépatite E</term><term>Interféron gamma</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Hépatite E</term><term>Lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Hepatitis E</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>T-Cell Antigen Receptor Specificity</term><term>Time Factors</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Facteurs temps</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Spécificité antigénique des récepteurs des lymphocytes T</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4(+) /CD8(+) T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/10(6) peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8(+) T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8(+) responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4(+) and CD8(+) T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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