T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice.
Identifieur interne : 002432 ( Main/Exploration ); précédent : 002431; suivant : 002433T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice.
Auteurs : Jincun Zhao [États-Unis] ; Jingxian Zhao ; Stanley PerlmanSource :
- Journal of virology [ 1098-5514 ] ; 2010.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Lymphocytes T (immunologie), Poumon (virologie), Rate (immunologie), Souris, Souris SCID, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (immunologie), Transfert adoptif, Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Virus du SRAS (immunologie).
- MESH :
- administration et posologie : Vaccins antiviraux.
- anatomopathologie : Syndrome respiratoire aigu sévère.
- immunologie : Lymphocytes T, Rate, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Virus du SRAS.
- virologie : Poumon.
- Analyse de survie, Animaux, Souris, Souris SCID, Souris de lignée BALB C, Syndrome respiratoire aigu sévère, Transfert adoptif.
English descriptors
- KwdEn :
- Adoptive Transfer, Animals, Lung (virology), Mice, Mice, Inbred BALB C, Mice, SCID, SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (prevention & control), Spleen (immunology), Survival Analysis, T-Lymphocytes (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Viral Vaccines.
- immunology : SARS Virus, Severe Acute Respiratory Syndrome, Spleen, T-Lymphocytes, Viral Vaccines.
- pathology : Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Lung.
- Adoptive Transfer, Animals, Mice, Mice, Inbred BALB C, Mice, SCID, Survival Analysis.
Abstract
A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.
DOI: 10.1128/JVI.01049-10
PubMed: 20610717
Affiliations:
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type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Zhao, Jingxian" sort="Zhao, Jingxian" uniqKey="Zhao J" first="Jingxian" last="Zhao">Jingxian Zhao</name></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adoptive Transfer</term><term>Animals</term><term>Lung (virology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term><term>SARS Virus (immunology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (pathology)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Spleen (immunology)</term><term>Survival Analysis</term><term>T-Lymphocytes (immunology)</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Lymphocytes T (immunologie)</term><term>Poumon (virologie)</term><term>Rate (immunologie)</term><term>Souris</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (anatomopathologie)</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Transfert adoptif</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Virus du SRAS (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T</term><term>Rate</term><term>Syndrome respiratoire aigu sévère</term><term>Vaccins antiviraux</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term><term>Spleen</term><term>T-Lymphocytes</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adoptive Transfer</term><term>Animals</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, SCID</term><term>Survival Analysis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Souris</term><term>Souris SCID</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère</term><term>Transfert adoptif</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.</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><noCountry><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Zhao, Jingxian" sort="Zhao, Jingxian" uniqKey="Zhao J" first="Jingxian" last="Zhao">Jingxian Zhao</name></noCountry><country name="États-Unis"><region name="Iowa"><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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