Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.
Identifieur interne : 000C62 ( Main/Exploration ); précédent : 000C61; suivant : 000C63Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.
Auteurs : Megan E. Schmidt [États-Unis] ; Cory J. Knudson [États-Unis] ; Stacey M. Hartwig [États-Unis] ; Lecia L. Pewe [États-Unis] ; David K. Meyerholz [États-Unis] ; Ryan A. Langlois [États-Unis] ; John T. Harty [États-Unis] ; Steven M. Varga [États-Unis]Source :
- PLoS pathogens [ 1553-7374 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Cellules cultivées, Femelle, Humains, Indice de gravité médicale, Infections à virus respiratoire syncytial (), Infections à virus respiratoire syncytial (anatomopathologie), Infections à virus respiratoire syncytial (immunologie), Lymphocytes T CD8+ (physiologie), Maladies du système immunitaire (anatomopathologie), Maladies du système immunitaire (immunologie), Maladies du système immunitaire (virologie), Mémoire immunologique, Souris, Souris de lignée BALB C, Virus respiratoires syncytiaux (immunologie).
- MESH :
- anatomopathologie : Infections à virus respiratoire syncytial, Maladies du système immunitaire.
- immunologie : Infections à virus respiratoire syncytial, Maladies du système immunitaire, Virus respiratoires syncytiaux.
- physiologie : Lymphocytes T CD8+.
- virologie : Maladies du système immunitaire.
- Animaux, Cellules cultivées, Femelle, Humains, Indice de gravité médicale, Infections à virus respiratoire syncytial, Mémoire immunologique, Souris, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Animals, CD8-Positive T-Lymphocytes (physiology), Cells, Cultured, Female, Humans, Immune System Diseases (immunology), Immune System Diseases (pathology), Immune System Diseases (virology), Immunologic Memory, Mice, Mice, Inbred BALB C, Respiratory Syncytial Virus Infections (complications), Respiratory Syncytial Virus Infections (immunology), Respiratory Syncytial Virus Infections (pathology), Respiratory Syncytial Viruses (immunology), Severity of Illness Index.
- MESH :
- complications : Respiratory Syncytial Virus Infections.
- immunology : Immune System Diseases, Respiratory Syncytial Virus Infections, Respiratory Syncytial Viruses.
- pathology : Immune System Diseases, Respiratory Syncytial Virus Infections.
- physiology : CD8-Positive T-Lymphocytes.
- virology : Immune System Diseases.
- Animals, Cells, Cultured, Female, Humans, Immunologic Memory, Mice, Mice, Inbred BALB C, Severity of Illness Index.
Abstract
Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.
DOI: 10.1371/journal.ppat.1006810
PubMed: 29293660
Affiliations:
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Schmidt</name><affiliation wicri:level="4"><nlm:affiliation>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Knudson, Cory J" sort="Knudson, Cory J" uniqKey="Knudson C" first="Cory J" last="Knudson">Cory J. Knudson</name><affiliation wicri:level="4"><nlm:affiliation>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Hartwig, Stacey M" sort="Hartwig, Stacey M" uniqKey="Hartwig S" first="Stacey M" last="Hartwig">Stacey M. Hartwig</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Pewe, Lecia L" sort="Pewe, Lecia L" uniqKey="Pewe L" first="Lecia L" last="Pewe">Lecia L. 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Meyerholz</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Langlois, Ryan A" sort="Langlois, Ryan A" uniqKey="Langlois R" first="Ryan A" last="Langlois">Ryan A. Langlois</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Harty, John T" sort="Harty, John T" uniqKey="Harty J" first="John T" last="Harty">John T. Harty</name><affiliation wicri:level="4"><nlm:affiliation>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Varga, Steven M" sort="Varga, Steven M" uniqKey="Varga S" first="Steven M" last="Varga">Steven M. Varga</name><affiliation wicri:level="4"><nlm:affiliation>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author></analytic><series><title level="j">PLoS pathogens</title><idno type="eISSN">1553-7374</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>CD8-Positive T-Lymphocytes (physiology)</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Immune System Diseases (immunology)</term><term>Immune System Diseases (pathology)</term><term>Immune System Diseases (virology)</term><term>Immunologic Memory</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Respiratory Syncytial Virus Infections (complications)</term><term>Respiratory Syncytial Virus Infections (immunology)</term><term>Respiratory Syncytial Virus Infections (pathology)</term><term>Respiratory Syncytial Viruses (immunology)</term><term>Severity of Illness Index</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Indice de gravité médicale</term><term>Infections à virus respiratoire syncytial ()</term><term>Infections à virus respiratoire syncytial (anatomopathologie)</term><term>Infections à virus respiratoire syncytial (immunologie)</term><term>Lymphocytes T CD8+ (physiologie)</term><term>Maladies du système immunitaire (anatomopathologie)</term><term>Maladies du système immunitaire (immunologie)</term><term>Maladies du système immunitaire (virologie)</term><term>Mémoire immunologique</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Virus respiratoires syncytiaux (immunologie)</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à virus respiratoire syncytial</term><term>Maladies du système immunitaire</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Respiratory Syncytial Virus Infections</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à virus respiratoire syncytial</term><term>Maladies du système immunitaire</term><term>Virus respiratoires syncytiaux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Immune System Diseases</term><term>Respiratory Syncytial Virus Infections</term><term>Respiratory Syncytial Viruses</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Immune System Diseases</term><term>Respiratory Syncytial Virus Infections</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Maladies du système immunitaire</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Immune System Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Female</term><term>Humans</term><term>Immunologic Memory</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Severity of Illness Index</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Indice de gravité médicale</term><term>Infections à virus respiratoire syncytial</term><term>Mémoire immunologique</term><term>Souris</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Iowa</li><li>Minnesota</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Schmidt, Megan E" sort="Schmidt, Megan E" uniqKey="Schmidt M" first="Megan E" last="Schmidt">Megan E. Schmidt</name></region><name sortKey="Hartwig, Stacey M" sort="Hartwig, Stacey M" uniqKey="Hartwig S" first="Stacey M" last="Hartwig">Stacey M. Hartwig</name><name sortKey="Harty, John T" sort="Harty, John T" uniqKey="Harty J" first="John T" last="Harty">John T. Harty</name><name sortKey="Knudson, Cory J" sort="Knudson, Cory J" uniqKey="Knudson C" first="Cory J" last="Knudson">Cory J. Knudson</name><name sortKey="Langlois, Ryan A" sort="Langlois, Ryan A" uniqKey="Langlois R" first="Ryan A" last="Langlois">Ryan A. Langlois</name><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K" last="Meyerholz">David K. Meyerholz</name><name sortKey="Pewe, Lecia L" sort="Pewe, Lecia L" uniqKey="Pewe L" first="Lecia L" last="Pewe">Lecia L. Pewe</name><name sortKey="Varga, Steven M" sort="Varga, Steven M" uniqKey="Varga S" first="Steven M" last="Varga">Steven M. Varga</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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