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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 : 000612

Effect 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 :

RBID : pubmed:29222166

Descripteurs français

English descriptors

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:


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Le document en format XML

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<name sortKey="Croughs, Therese" sort="Croughs, Therese" uniqKey="Croughs T" first="Thérèse" last="Croughs">Thérèse Croughs</name>
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<name sortKey="Lederman, Michael M" sort="Lederman, Michael M" uniqKey="Lederman M" first="Michael M" last="Lederman">Michael M. Lederman</name>
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<region type="state">Ohio</region>
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<name sortKey="Sereti, Irini" sort="Sereti, Irini" uniqKey="Sereti I" first="Irini" last="Sereti">Irini Sereti</name>
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<region type="state">Maryland</region>
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<name sortKey="Fischl, Margaret A" sort="Fischl, Margaret A" uniqKey="Fischl M" first="Margaret A" last="Fischl">Margaret A. Fischl</name>
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<region type="state">Floride</region>
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<name sortKey="Watts, Tania H" sort="Watts, Tania H" uniqKey="Watts T" first="Tania H" last="Watts">Tania H. Watts</name>
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<name sortKey="Wang, Chao" sort="Wang, Chao" uniqKey="Wang C" first="Chao" last="Wang">Chao Wang</name>
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<nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</nlm:affiliation>
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<settlement type="city">Toronto</settlement>
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<name sortKey="Edilova, Maria I" sort="Edilova, Maria I" uniqKey="Edilova M" first="Maria I" last="Edilova">Maria I. Edilova</name>
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<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>
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<settlement type="city">Toronto</settlement>
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</placeName>
</affiliation>
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<name sortKey="Wagar, Lisa E" sort="Wagar, Lisa E" uniqKey="Wagar L" first="Lisa E" last="Wagar">Lisa E. Wagar</name>
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<nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
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<name sortKey="Mujib, Shariq" sort="Mujib, Shariq" uniqKey="Mujib S" first="Shariq" last="Mujib">Shariq Mujib</name>
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<nlm:affiliation>Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
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<orgName type="university">Université de Toronto</orgName>
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<name sortKey="Singer, Meromit" sort="Singer, Meromit" uniqKey="Singer M" first="Meromit" last="Singer">Meromit Singer</name>
<affiliation wicri:level="2">
<nlm:affiliation>Broad Institute, Cambridge, MA 02142.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Broad Institute, Cambridge</wicri:cityArea>
</affiliation>
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<name sortKey="Bernard, Nicole F" sort="Bernard, Nicole F" uniqKey="Bernard N" first="Nicole F" last="Bernard">Nicole F. Bernard</name>
<affiliation wicri:level="1">
<nlm:affiliation>Chronic Viral Illness Service, Division of Clinical Immunology, Research Institute, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Chronic Viral Illness Service, Division of Clinical Immunology, Research Institute, McGill University Health Centre, Montreal, Quebec H3G 1A4</wicri:regionArea>
<wicri:noRegion>Quebec H3G 1A4</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Croughs, Therese" sort="Croughs, Therese" uniqKey="Croughs T" first="Thérèse" last="Croughs">Thérèse Croughs</name>
<affiliation wicri:level="3">
<nlm:affiliation>Agence Nationale de Recherches sur le SIDA, 75013 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Agence Nationale de Recherches sur le SIDA, 75013 Paris</wicri:regionArea>
<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>
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<name sortKey="Fischl, Margaret A" sort="Fischl, Margaret A" uniqKey="Fischl M" first="Margaret A" last="Fischl">Margaret A. Fischl</name>
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<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>
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<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>
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<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
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<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>
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<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>
<orgName type="university">Université McGill</orgName>
<placeName>
<settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Watts, Tania H" sort="Watts, Tania H" uniqKey="Watts T" first="Tania H" last="Watts">Tania H. Watts</name>
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<nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; tania.watts@utoronto.ca.</nlm:affiliation>
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<settlement type="city">Toronto</settlement>
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<series>
<title level="j">Journal of immunology (Baltimore, Md. : 1950)</title>
<idno type="eISSN">1550-6606</idno>
<imprint>
<date when="2018" type="published">2018</date>
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<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>
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<term>Cytokines</term>
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<term>Cytokines</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>HIV Infections</term>
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<term>TNF Receptor-Associated Factor 1</term>
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<term>Facteur-1 associé aux récepteurs de TNF</term>
<term>Protéine ribosomique S6</term>
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<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>
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<term>CD8-Positive T-Lymphocytes</term>
<term>HIV Infections</term>
<term>HIV-1</term>
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<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>
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<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>
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<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>
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<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>
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<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>
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<Year>2019</Year>
<Month>10</Month>
<Day>08</Day>
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<Journal>
<ISSN IssnType="Electronic">1550-6606</ISSN>
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<Volume>200</Volume>
<Issue>2</Issue>
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<Day>15</Day>
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<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>
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<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>
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<Affiliation>Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.</Affiliation>
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<LastName>Edilova</LastName>
<ForeName>Maria I</ForeName>
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