Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.
Identifieur interne : 000611 ( Main/Exploration ); précédent : 000610; suivant : 000612Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.
Auteurs : Chao Wang [Canada] ; Maria I. Edilova [Canada] ; Lisa E. Wagar [Canada] ; Shariq Mujib [Canada] ; Meromit Singer [États-Unis] ; Nicole F. Bernard [Canada] ; Thérèse Croughs [France] ; Michael M. Lederman [États-Unis] ; Irini Sereti [États-Unis] ; Margaret A. Fischl [États-Unis] ; Elisabeth Kremmer [Allemagne] ; Mario Ostrowski [Canada] ; Jean-Pierre Routy [Canada] ; Tania H. Watts [Canada]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2018.
Descripteurs français
- KwdFr :
- Charge virale (MeSH), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Cytokines (biosynthèse), Expression des gènes (MeSH), Facteur-1 associé aux récepteurs de TNF (génétique), Facteur-1 associé aux récepteurs de TNF (métabolisme), Humains (MeSH), Infections à VIH (immunologie), Infections à VIH (métabolisme), Infections à VIH (traitement médicamenteux), Infections à VIH (virologie), Interleukine-7 (pharmacologie), Interleukine-7 (usage thérapeutique), Liaison aux protéines (MeSH), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (métabolisme), Numération des lymphocytes (MeSH), Numération des lymphocytes CD4 (MeSH), Protéine ribosomique S6 (génétique), Protéine ribosomique S6 (métabolisme), Protéines recombinantes (pharmacologie), Protéines recombinantes (usage thérapeutique), Récepteur cellulaire-2 du virus de l'hépatite A (métabolisme), Récepteur-1 de mort cellulaire programmée (métabolisme), Thérapie antirétrovirale hautement active (MeSH), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie).
- MESH :
- biosynthèse : Cytokines.
- génétique : Facteur-1 associé aux récepteurs de TNF, Protéine ribosomique S6.
- immunologie : Infections à VIH, Lymphocytes T CD8+, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : Complexe-1 cible mécanistique de la rapamycine, Facteur-1 associé aux récepteurs de TNF, Infections à VIH, Lymphocytes T CD8+, Protéine ribosomique S6, Récepteur cellulaire-2 du virus de l'hépatite A, Récepteur-1 de mort cellulaire programmée.
- pharmacologie : Interleukine-7, Protéines recombinantes.
- traitement médicamenteux : Infections à VIH.
- usage thérapeutique : Interleukine-7, Protéines recombinantes.
- virologie : Infections à VIH.
- Charge virale, Expression des gènes, Humains, Liaison aux protéines, Numération des lymphocytes, Numération des lymphocytes CD4, Thérapie antirétrovirale hautement active.
English descriptors
- KwdEn :
- Antiretroviral Therapy, Highly Active (MeSH), CD4 Lymphocyte Count (MeSH), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (metabolism), Cytokines (biosynthesis), Gene Expression (MeSH), HIV Infections (drug therapy), HIV Infections (immunology), HIV Infections (metabolism), HIV Infections (virology), HIV-1 (immunology), Hepatitis A Virus Cellular Receptor 2 (metabolism), Humans (MeSH), Interleukin-7 (pharmacology), Interleukin-7 (therapeutic use), Lymphocyte Count (MeSH), Mechanistic Target of Rapamycin Complex 1 (metabolism), Programmed Cell Death 1 Receptor (metabolism), Protein Binding (MeSH), Recombinant Proteins (pharmacology), Recombinant Proteins (therapeutic use), Ribosomal Protein S6 (genetics), Ribosomal Protein S6 (metabolism), TNF Receptor-Associated Factor 1 (genetics), TNF Receptor-Associated Factor 1 (metabolism), Viral Load (MeSH).
- MESH :
- chemical , biosynthesis : Cytokines.
- drug therapy : HIV Infections.
- chemical , genetics : Ribosomal Protein S6, TNF Receptor-Associated Factor 1.
- immunology : CD8-Positive T-Lymphocytes, HIV Infections, HIV-1.
- metabolism : CD8-Positive T-Lymphocytes, HIV Infections, Hepatitis A Virus Cellular Receptor 2, Mechanistic Target of Rapamycin Complex 1, Programmed Cell Death 1 Receptor, Ribosomal Protein S6, TNF Receptor-Associated Factor 1.
- chemical , pharmacology : Interleukin-7, Recombinant Proteins.
- chemical , therapeutic use : Interleukin-7, Recombinant Proteins.
- virology : HIV Infections.
- Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Gene Expression, Humans, Lymphocyte Count, Protein Binding, Viral Load.
Abstract
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice. Previous results showed that IL-7 can restore TRAF1 expression in virus-specific CD8 T cells in mice, rendering them sensitive to anti-4-1BB agonist therapy. In this article, we show that IL-7 therapy in humans increases the number of circulating HIV-specific CD8 T cells. For a subset of patients, we also observed an increased frequency of TRAF1+ HIV-specific CD8 T cells 10 wk after completion of IL-7 treatment. IL-7 treatment increased levels of phospho-ribosomal protein S6 in HIV-specific CD8 T cells, suggesting increased activation of the metabolic checkpoint kinase mTORC1. Thus, IL-7 therapy in antiretroviral therapy-treated patients induces sustained changes in the number and phenotype of HIV-specific T cells.
DOI: 10.4049/jimmunol.1601254
PubMed: 29222166
PubMed Central: PMC5760332
Affiliations:
- Allemagne, Canada, France, États-Unis
- Bavière, District de Haute-Bavière, Floride, Maryland, Massachusetts, Ohio, Ontario, Québec, Île-de-France
- Montréal, Munich, Paris, Toronto
- Université McGill, Université de Toronto
Links toward previous steps (curation, corpus...)
Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.</title>
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<author><name sortKey="Singer, Meromit" sort="Singer, Meromit" uniqKey="Singer M" first="Meromit" last="Singer">Meromit Singer</name>
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<author><name sortKey="Bernard, Nicole F" sort="Bernard, Nicole F" uniqKey="Bernard N" first="Nicole F" last="Bernard">Nicole F. Bernard</name>
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<wicri:regionArea>Chronic Viral Illness Service, Division of Clinical Immunology, Research Institute, McGill University Health Centre, Montreal, Quebec H3G 1A4</wicri:regionArea>
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<author><name sortKey="Croughs, Therese" sort="Croughs, Therese" uniqKey="Croughs T" first="Thérèse" last="Croughs">Thérèse Croughs</name>
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<country xml:lang="fr">France</country>
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<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lederman, Michael M" sort="Lederman, Michael M" uniqKey="Lederman M" first="Michael M" last="Lederman">Michael M. Lederman</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for AIDS Research, Case Western Reserve University School of Medicine, Cleveland, OH 44106.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>Center for AIDS Research, Case Western Reserve University School of Medicine, Cleveland</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sereti, Irini" sort="Sereti, Irini" uniqKey="Sereti I" first="Irini" last="Sereti">Irini Sereti</name>
<affiliation wicri:level="2"><nlm:affiliation>National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Fischl, Margaret A" sort="Fischl, Margaret A" uniqKey="Fischl M" first="Margaret A" last="Fischl">Margaret A. Fischl</name>
<affiliation wicri:level="2"><nlm:affiliation>Miami Center for AIDS Research, University of Miami School of Medicine, Miami, FL 33136.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Floride</region>
</placeName>
<wicri:cityArea>Miami Center for AIDS Research, University of Miami School of Medicine, Miami</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kremmer, Elisabeth" sort="Kremmer, Elisabeth" uniqKey="Kremmer E" first="Elisabeth" last="Kremmer">Elisabeth Kremmer</name>
<affiliation wicri:level="3"><nlm:affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health, 81377 Munich, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München, German Research Centre for Environmental Health, 81377 Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ostrowski, Mario" sort="Ostrowski, Mario" uniqKey="Ostrowski M" first="Mario" last="Ostrowski">Mario Ostrowski</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:affiliation>Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario M5B1W8, Canada; and.</nlm:affiliation>
<wicri:noCountry code="subField">Canada; and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Routy, Jean Pierre" sort="Routy, Jean Pierre" uniqKey="Routy J" first="Jean-Pierre" last="Routy">Jean-Pierre Routy</name>
<affiliation wicri:level="4"><nlm:affiliation>Division of Hematology and Immunodeficiency Service, McGill University, Montreal, Quebec H3A 1A3, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Hematology and Immunodeficiency Service, McGill University, Montreal, Quebec H3A 1A3</wicri:regionArea>
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<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
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<author><name sortKey="Watts, Tania H" sort="Watts, Tania H" uniqKey="Watts T" first="Tania H" last="Watts">Tania H. Watts</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; tania.watts@utoronto.ca.</nlm:affiliation>
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</affiliation>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiretroviral Therapy, Highly Active (MeSH)</term>
<term>CD4 Lymphocyte Count (MeSH)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (metabolism)</term>
<term>Cytokines (biosynthesis)</term>
<term>Gene Expression (MeSH)</term>
<term>HIV Infections (drug therapy)</term>
<term>HIV Infections (immunology)</term>
<term>HIV Infections (metabolism)</term>
<term>HIV Infections (virology)</term>
<term>HIV-1 (immunology)</term>
<term>Hepatitis A Virus Cellular Receptor 2 (metabolism)</term>
<term>Humans (MeSH)</term>
<term>Interleukin-7 (pharmacology)</term>
<term>Interleukin-7 (therapeutic use)</term>
<term>Lymphocyte Count (MeSH)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term>
<term>Programmed Cell Death 1 Receptor (metabolism)</term>
<term>Protein Binding (MeSH)</term>
<term>Recombinant Proteins (pharmacology)</term>
<term>Recombinant Proteins (therapeutic use)</term>
<term>Ribosomal Protein S6 (genetics)</term>
<term>Ribosomal Protein S6 (metabolism)</term>
<term>TNF Receptor-Associated Factor 1 (genetics)</term>
<term>TNF Receptor-Associated Factor 1 (metabolism)</term>
<term>Viral Load (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Charge virale (MeSH)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Cytokines (biosynthèse)</term>
<term>Expression des gènes (MeSH)</term>
<term>Facteur-1 associé aux récepteurs de TNF (génétique)</term>
<term>Facteur-1 associé aux récepteurs de TNF (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Infections à VIH (immunologie)</term>
<term>Infections à VIH (métabolisme)</term>
<term>Infections à VIH (traitement médicamenteux)</term>
<term>Infections à VIH (virologie)</term>
<term>Interleukine-7 (pharmacologie)</term>
<term>Interleukine-7 (usage thérapeutique)</term>
<term>Liaison aux protéines (MeSH)</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T CD8+ (métabolisme)</term>
<term>Numération des lymphocytes (MeSH)</term>
<term>Numération des lymphocytes CD4 (MeSH)</term>
<term>Protéine ribosomique S6 (génétique)</term>
<term>Protéine ribosomique S6 (métabolisme)</term>
<term>Protéines recombinantes (pharmacologie)</term>
<term>Protéines recombinantes (usage thérapeutique)</term>
<term>Récepteur cellulaire-2 du virus de l'hépatite A (métabolisme)</term>
<term>Récepteur-1 de mort cellulaire programmée (métabolisme)</term>
<term>Thérapie antirétrovirale hautement active (MeSH)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Ribosomal Protein S6</term>
<term>TNF Receptor-Associated Factor 1</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur-1 associé aux récepteurs de TNF</term>
<term>Protéine ribosomique S6</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à VIH</term>
<term>Lymphocytes T CD8+</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>HIV Infections</term>
<term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>HIV Infections</term>
<term>Hepatitis A Virus Cellular Receptor 2</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Programmed Cell Death 1 Receptor</term>
<term>Ribosomal Protein S6</term>
<term>TNF Receptor-Associated Factor 1</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Facteur-1 associé aux récepteurs de TNF</term>
<term>Infections à VIH</term>
<term>Lymphocytes T CD8+</term>
<term>Protéine ribosomique S6</term>
<term>Récepteur cellulaire-2 du virus de l'hépatite A</term>
<term>Récepteur-1 de mort cellulaire programmée</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Interleukine-7</term>
<term>Protéines recombinantes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Interleukin-7</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Interleukin-7</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Interleukine-7</term>
<term>Protéines recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Antiretroviral Therapy, Highly Active</term>
<term>CD4 Lymphocyte Count</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Lymphocyte Count</term>
<term>Protein Binding</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Charge virale</term>
<term>Expression des gènes</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Numération des lymphocytes</term>
<term>Numération des lymphocytes CD4</term>
<term>Thérapie antirétrovirale hautement active</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice. Previous results showed that IL-7 can restore TRAF1 expression in virus-specific CD8 T cells in mice, rendering them sensitive to anti-4-1BB agonist therapy. In this article, we show that IL-7 therapy in humans increases the number of circulating HIV-specific CD8 T cells. For a subset of patients, we also observed an increased frequency of TRAF1<sup>+</sup>
HIV-specific CD8 T cells 10 wk after completion of IL-7 treatment. IL-7 treatment increased levels of phospho-ribosomal protein S6 in HIV-specific CD8 T cells, suggesting increased activation of the metabolic checkpoint kinase mTORC1. Thus, IL-7 therapy in antiretroviral therapy-treated patients induces sustained changes in the number and phenotype of HIV-specific T cells.</div>
</front>
</TEI>
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<DateCompleted><Year>2018</Year>
<Month>08</Month>
<Day>29</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>10</Month>
<Day>08</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1550-6606</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>200</Volume>
<Issue>2</Issue>
<PubDate><Year>2018</Year>
<Month>01</Month>
<Day>15</Day>
</PubDate>
</JournalIssue>
<Title>Journal of immunology (Baltimore, Md. : 1950)</Title>
<ISOAbbreviation>J Immunol</ISOAbbreviation>
</Journal>
<ArticleTitle>Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.</ArticleTitle>
<Pagination><MedlinePgn>558-564</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.4049/jimmunol.1601254</ELocationID>
<Abstract><AbstractText>IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice. Previous results showed that IL-7 can restore TRAF1 expression in virus-specific CD8 T cells in mice, rendering them sensitive to anti-4-1BB agonist therapy. In this article, we show that IL-7 therapy in humans increases the number of circulating HIV-specific CD8 T cells. For a subset of patients, we also observed an increased frequency of TRAF1<sup>+</sup>
HIV-specific CD8 T cells 10 wk after completion of IL-7 treatment. IL-7 treatment increased levels of phospho-ribosomal protein S6 in HIV-specific CD8 T cells, suggesting increased activation of the metabolic checkpoint kinase mTORC1. Thus, IL-7 therapy in antiretroviral therapy-treated patients induces sustained changes in the number and phenotype of HIV-specific T cells.</AbstractText>
<CopyrightInformation>Copyright © 2018 by The American Association of Immunologists, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Chao</ForeName>
<Initials>C</Initials>
<Identifier Source="ORCID">0000-0003-3084-6093</Identifier>
<AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Edilova</LastName>
<ForeName>Maria I</ForeName>
<Initials>MI</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wagar</LastName>
<ForeName>Lisa E</ForeName>
<Initials>LE</Initials>
<AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mujib</LastName>
<ForeName>Shariq</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">0000-0002-6206-5622</Identifier>
<AffiliationInfo><Affiliation>Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Singer</LastName>
<ForeName>Meromit</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Broad Institute, Cambridge, MA 02142.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bernard</LastName>
<ForeName>Nicole F</ForeName>
<Initials>NF</Initials>
<AffiliationInfo><Affiliation>Chronic Viral Illness Service, Division of Clinical Immunology, Research Institute, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Croughs</LastName>
<ForeName>Thérèse</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0003-0246-7619</Identifier>
<AffiliationInfo><Affiliation>Agence Nationale de Recherches sur le SIDA, 75013 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lederman</LastName>
<ForeName>Michael M</ForeName>
<Initials>MM</Initials>
<AffiliationInfo><Affiliation>Center for AIDS Research, Case Western Reserve University School of Medicine, Cleveland, OH 44106.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sereti</LastName>
<ForeName>Irini</ForeName>
<Initials>I</Initials>
<Identifier Source="ORCID">0000-0002-0076-0224</Identifier>
<AffiliationInfo><Affiliation>National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fischl</LastName>
<ForeName>Margaret A</ForeName>
<Initials>MA</Initials>
<Identifier Source="ORCID">0000-0001-9241-5390</Identifier>
<AffiliationInfo><Affiliation>Miami Center for AIDS Research, University of Miami School of Medicine, Miami, FL 33136.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kremmer</LastName>
<ForeName>Elisabeth</ForeName>
<Initials>E</Initials>
<Identifier Source="ORCID">0000-0002-8133-8374</Identifier>
<AffiliationInfo><Affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health, 81377 Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ostrowski</LastName>
<ForeName>Mario</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0002-7369-1936</Identifier>
<AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario M5B1W8, Canada; and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Routy</LastName>
<ForeName>Jean-Pierre</ForeName>
<Initials>JP</Initials>
<Identifier Source="ORCID">0000-0001-9897-7589</Identifier>
<AffiliationInfo><Affiliation>Division of Hematology and Immunodeficiency Service, McGill University, Montreal, Quebec H3A 1A3, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Watts</LastName>
<ForeName>Tania H</ForeName>
<Initials>TH</Initials>
<Identifier Source="ORCID">0000-0001-7897-4890</Identifier>
<AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; tania.watts@utoronto.ca.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>UM1 AI069501</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Agency>Intramural NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>THA-11906</GrantID>
<Agency>CIHR</Agency>
<Country>Canada</Country>
</Grant>
<Grant><GrantID>FDN 143250 </GrantID>
<Agency>CIHR</Agency>
<Country>Canada</Country>
</Grant>
<Grant><GrantID>U01 AI069501</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>MOP-74492</GrantID>
<Agency>CIHR</Agency>
<Country>Canada</Country>
</Grant>
<Grant><GrantID>P30 AI036219</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Agency>CIHR</Agency>
<Country>Canada</Country>
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<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>12</Month>
<Day>08</Day>
</ArticleDate>
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<MedlineTA>J Immunol</MedlineTA>
<NlmUniqueID>2985117R</NlmUniqueID>
<ISSNLinking>0022-1767</ISSNLinking>
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<NameOfSubstance UI="D016207">Cytokines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C448908">HAVCR2 protein, human</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000072597">Hepatitis A Virus Cellular Receptor 2</NameOfSubstance>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D018791" MajorTopicYN="N">CD4 Lymphocyte Count</DescriptorName>
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<MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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<MeshHeading><DescriptorName UI="D018655" MajorTopicYN="N">Lymphocyte Count</DescriptorName>
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<MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D038601" MajorTopicYN="N">Ribosomal Protein S6</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047990" MajorTopicYN="N">TNF Receptor-Associated Factor 1</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName>
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