Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection
Identifieur interne : 001532 ( Main/Exploration ); précédent : 001531; suivant : 001533Virus-Specific Memory CD8 T Cells Provide Substantial Protection from Lethal Severe Acute Respiratory Syndrome Coronavirus Infection
Auteurs : Rudragouda Channappanavar [États-Unis] ; Craig Fett [États-Unis] ; Jincun Zhao [États-Unis] ; David K. Meyerholz [États-Unis] ; Stanley Perlman [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2014.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Anticorps antiviraux (biosynthèse), Antigènes viraux (), Antigènes viraux (génétique), Antigènes viraux (immunologie), Cellules dendritiques (immunologie), Cellules dendritiques (transplantation), Cellules dendritiques (virologie), Déterminants antigéniques des lymphocytes T (génétique), Déterminants antigéniques des lymphocytes T (immunologie), Expression des gènes, Femelle, Humains, Immunisation, Immunité active, Immunité cellulaire (), Immunité humorale (), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (virologie), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (virologie), Mémoire immunologique, Peptides (administration et posologie), Peptides (génétique), Peptides (immunologie), Souris, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (mortalité), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (immunologie), Virus du SRAS (pathogénicité).
- MESH :
- administration et posologie : Peptides.
- biosynthèse : Anticorps antiviraux.
- génétique : Antigènes viraux, Déterminants antigéniques des lymphocytes T, Peptides.
- immunologie : Antigènes viraux, Cellules dendritiques, Déterminants antigéniques des lymphocytes T, Lymphocytes T CD4+, Lymphocytes T CD8+, Peptides, Syndrome respiratoire aigu sévère, Virus du SRAS.
- mortalité : Syndrome respiratoire aigu sévère.
- pathogénicité : Virus du SRAS.
- virologie : Cellules dendritiques, Lymphocytes T CD4+, Lymphocytes T CD8+, Syndrome respiratoire aigu sévère.
- Analyse de survie, Animaux, Antigènes viraux, Cellules dendritiques, Expression des gènes, Femelle, Humains, Immunisation, Immunité active, Immunité cellulaire, Immunité humorale, Mémoire immunologique, Souris, Syndrome respiratoire aigu sévère.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (biosynthesis), Antigens, Viral (chemistry), Antigens, Viral (genetics), Antigens, Viral (immunology), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (virology), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (virology), Dendritic Cells (immunology), Dendritic Cells (transplantation), Dendritic Cells (virology), Epitopes, T-Lymphocyte (genetics), Epitopes, T-Lymphocyte (immunology), Female, Gene Expression, Humans, Immunity, Active, Immunity, Cellular (drug effects), Immunity, Humoral (drug effects), Immunization, Immunologic Memory, Mice, Peptides (administration & dosage), Peptides (genetics), Peptides (immunology), SARS Virus (immunology), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (mortality), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Survival Analysis.
- MESH :
- chemical , administration & dosage : Peptides.
- chemical , biosynthesis : Antibodies, Viral.
- chemical , chemistry : Antigens, Viral.
- chemical , genetics : Antigens, Viral, Epitopes, T-Lymphocyte, Peptides.
- chemical , immunology : Antigens, Viral, Epitopes, T-Lymphocyte, Peptides.
- drug effects : Immunity, Cellular, Immunity, Humoral.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Dendritic Cells, SARS Virus, Severe Acute Respiratory Syndrome.
- mortality : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- transplantation : Dendritic Cells.
- virology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Dendritic Cells, Severe Acute Respiratory Syndrome.
- Animals, Female, Gene Expression, Humans, Immunity, Active, Immunization, Immunologic Memory, Mice, Survival Analysis.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection.
Url:
DOI: 10.1128/JVI.01505-14
PubMed: 25056892
PubMed Central: 4178831
Affiliations:
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Le document en format XML
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Meyerholz</name><affiliation wicri:level="4"><nlm:aff id="aff2">Department of Pathology, University of Iowa, Iowa City, Iowa, USA</nlm:aff><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="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Microbiology, University of Iowa, Iowa City, Iowa, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, 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">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Viral (biosynthesis)</term><term>Antigens, Viral (chemistry)</term><term>Antigens, Viral (genetics)</term><term>Antigens, Viral (immunology)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD4-Positive T-Lymphocytes (virology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>CD8-Positive T-Lymphocytes (virology)</term><term>Dendritic Cells (immunology)</term><term>Dendritic Cells (transplantation)</term><term>Dendritic Cells (virology)</term><term>Epitopes, T-Lymphocyte (genetics)</term><term>Epitopes, T-Lymphocyte (immunology)</term><term>Female</term><term>Gene Expression</term><term>Humans</term><term>Immunity, Active</term><term>Immunity, Cellular (drug effects)</term><term>Immunity, Humoral (drug effects)</term><term>Immunization</term><term>Immunologic Memory</term><term>Mice</term><term>Peptides (administration & dosage)</term><term>Peptides (genetics)</term><term>Peptides (immunology)</term><term>SARS Virus (immunology)</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (mortality)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Survival Analysis</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Anticorps antiviraux (biosynthèse)</term><term>Antigènes viraux ()</term><term>Antigènes viraux (génétique)</term><term>Antigènes viraux (immunologie)</term><term>Cellules dendritiques (immunologie)</term><term>Cellules dendritiques (transplantation)</term><term>Cellules dendritiques (virologie)</term><term>Déterminants antigéniques des lymphocytes T (génétique)</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Expression des gènes</term><term>Femelle</term><term>Humains</term><term>Immunisation</term><term>Immunité active</term><term>Immunité cellulaire ()</term><term>Immunité humorale ()</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes T CD4+ (virologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Lymphocytes T CD8+ (virologie)</term><term>Mémoire immunologique</term><term>Peptides (administration et posologie)</term><term>Peptides (génétique)</term><term>Peptides (immunologie)</term><term>Souris</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (mortalité)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antigens, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term><term>Epitopes, T-Lymphocyte</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>Epitopes, T-Lymphocyte</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Immunity, Cellular</term><term>Immunity, Humoral</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes viraux</term><term>Déterminants antigéniques des lymphocytes T</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term><term>Cellules dendritiques</term><term>Déterminants antigéniques des lymphocytes T</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term><term>Peptides</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>CD8-Positive T-Lymphocytes</term><term>Dendritic Cells</term><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Dendritic Cells</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules dendritiques</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>CD8-Positive T-Lymphocytes</term><term>Dendritic Cells</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Gene Expression</term><term>Humans</term><term>Immunity, Active</term><term>Immunization</term><term>Immunologic Memory</term><term>Mice</term><term>Survival Analysis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Antigènes viraux</term><term>Cellules dendritiques</term><term>Expression des gènes</term><term>Femelle</term><term>Humains</term><term>Immunisation</term><term>Immunité active</term><term>Immunité cellulaire</term><term>Immunité humorale</term><term>Mémoire immunologique</term><term>Souris</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection.</p><p><bold>IMPORTANCE</bold> Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Iowa</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="Channappanavar, Rudragouda" sort="Channappanavar, Rudragouda" uniqKey="Channappanavar R" first="Rudragouda" last="Channappanavar">Rudragouda Channappanavar</name></region><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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