T cell epitope specificity and pathogenesis of mouse hepatitis virus-1-induced disease in susceptible and resistant hosts.
Identifieur interne : 002433 ( Main/Exploration ); précédent : 002432; suivant : 002434T cell epitope specificity and pathogenesis of mouse hepatitis virus-1-induced disease in susceptible and resistant hosts.
Auteurs : Aaruni Khanolkar [États-Unis] ; Ross B. Fulton ; Lecia L. Epping ; Nhat-Long Pham ; Dilea Tifrea ; Steven M. Varga ; John T. HartySource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Déterminants antigéniques des lymphocytes T (immunologie), Femelle, Humains, Hépatite virale animale (immunologie), Immunité innée (immunologie), Infections à coronavirus (immunologie), Interféron gamma (métabolisme), Lignées consanguines de souris, Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (métabolisme), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (métabolisme), Modèles animaux de maladie humaine, Peptides (immunologie), Poumon (immunologie), Poumon (métabolisme), Poumon (virologie), Souris, Souris de lignée BALB C, Souris de lignée C3H, Souris de lignée C57BL, Spécificité d'espèce, Susceptibilité à une maladie (immunologie), Susceptibilité à une maladie (étiologie), Syndrome respiratoire aigu sévère (immunologie), Virus de l'hépatite murine (immunologie), Virus du SRAS (immunologie).
- MESH :
- immunologie : Déterminants antigéniques des lymphocytes T, Hépatite virale animale, Immunité innée, Infections à coronavirus, Lymphocytes T CD4+, Lymphocytes T CD8+, Peptides, Poumon, Susceptibilité à une maladie, Syndrome respiratoire aigu sévère, Virus de l'hépatite murine, Virus du SRAS.
- métabolisme : Interféron gamma, Lymphocytes T CD4+, Lymphocytes T CD8+, Poumon.
- virologie : Poumon.
- étiologie : Susceptibilité à une maladie.
- Animaux, Femelle, Humains, Lignées consanguines de souris, Modèles animaux de maladie humaine, Souris, Souris de lignée BALB C, Souris de lignée C3H, Souris de lignée C57BL, Spécificité d'espèce.
English descriptors
- KwdEn :
- Animals, CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (metabolism), Coronavirus Infections (immunology), Disease Models, Animal, Disease Susceptibility (etiology), Disease Susceptibility (immunology), Epitopes, T-Lymphocyte (immunology), Female, Hepatitis, Viral, Animal (immunology), Humans, Immunity, Innate (immunology), Interferon-gamma (metabolism), Lung (immunology), Lung (metabolism), Lung (virology), Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred Strains, Murine hepatitis virus (immunology), Peptides (immunology), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Species Specificity.
- MESH :
- chemical , immunology : Epitopes, T-Lymphocyte, Peptides.
- etiology : Disease Susceptibility.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Coronavirus Infections, Disease Susceptibility, Hepatitis, Viral, Animal, Immunity, Innate, Lung, Murine hepatitis virus, SARS Virus, Severe Acute Respiratory Syndrome.
- metabolism : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Interferon-gamma, Lung.
- virology : Lung.
- Animals, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred Strains, Species Specificity.
Abstract
Intranasal mouse hepatitis virus-1 (MHV-1) infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of severe acute respiratory syndrome (SARS)-coronavirus-infected humans. The pathogenesis of SARS remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. We previously reported that the adaptive immune response plays an important protective role in MHV-1-infected resistant B6 mice and that both CD4 and CD8 T cells play a significant role in the development of morbidity and lung pathology following intranasal MHV-1 infection of susceptible C3H/HeJ and A/J mice. In this study, we have identified novel CD4 and CD8 epitopes in MHV-1-infected susceptible and resistant strains of mice. Susceptible C3H/HeJ mice mount robust and broad MHV-1-specific CD4 T cell responses, whereas in resistant B6 mice, Ag-specific CD8 T cell responses dominate. We also show that previously immunized susceptible C3H/HeJ mice do not develop any morbidity and are completely protected following a lethal-dose MHV-1 challenge despite mounting only a modest secondary T cell response. Finally, we demonstrate that the resistance displayed by B6 mice is not solely accounted for by the elaboration of a broad and vigorous MHV-1-specific CD8 T cell response, as MHV-1 infection of C3.SW-H2(b)/SnJ mice, which mount an equally robust CD8 T cell response of the same specificity, is still associated with significant morbidity. Thus, identification of novel CD4 and CD8 T cell epitopes for MHV-1 permitted high-resolution analyses of pulmonary T cell responses in a mouse model of SARS.
DOI: 10.4049/jimmunol.0902749
PubMed: 20554960
Affiliations:
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(metabolism)</term><term>Lung (virology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C3H</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred Strains</term><term>Murine hepatitis virus (immunology)</term><term>Peptides (immunology)</term><term>SARS Virus (immunology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Species Specificity</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Femelle</term><term>Humains</term><term>Hépatite virale animale (immunologie)</term><term>Immunité innée (immunologie)</term><term>Infections à coronavirus (immunologie)</term><term>Interféron gamma (métabolisme)</term><term>Lignées consanguines de souris</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes T CD4+ (métabolisme)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Lymphocytes T CD8+ (métabolisme)</term><term>Modèles 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xml:lang="fr"><term>Interféron gamma</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term><term>Poumon</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" qualifier="étiologie" xml:lang="fr"><term>Susceptibilité à une maladie</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C3H</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred Strains</term><term>Species Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Lignées consanguines de souris</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C3H</term><term>Souris de lignée C57BL</term><term>Spécificité d'espèce</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Intranasal mouse hepatitis virus-1 (MHV-1) infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of severe acute respiratory syndrome (SARS)-coronavirus-infected humans. The pathogenesis of SARS remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. We previously reported that the adaptive immune response plays an important protective role in MHV-1-infected resistant B6 mice and that both CD4 and CD8 T cells play a significant role in the development of morbidity and lung pathology following intranasal MHV-1 infection of susceptible C3H/HeJ and A/J mice. In this study, we have identified novel CD4 and CD8 epitopes in MHV-1-infected susceptible and resistant strains of mice. Susceptible C3H/HeJ mice mount robust and broad MHV-1-specific CD4 T cell responses, whereas in resistant B6 mice, Ag-specific CD8 T cell responses dominate. We also show that previously immunized susceptible C3H/HeJ mice do not develop any morbidity and are completely protected following a lethal-dose MHV-1 challenge despite mounting only a modest secondary T cell response. Finally, we demonstrate that the resistance displayed by B6 mice is not solely accounted for by the elaboration of a broad and vigorous MHV-1-specific CD8 T cell response, as MHV-1 infection of C3.SW-H2(b)/SnJ mice, which mount an equally robust CD8 T cell response of the same specificity, is still associated with significant morbidity. Thus, identification of novel CD4 and CD8 T cell epitopes for MHV-1 permitted high-resolution analyses of pulmonary T cell responses in a mouse model of SARS.</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="Epping, Lecia L" sort="Epping, Lecia L" uniqKey="Epping L" first="Lecia L" last="Epping">Lecia L. Epping</name><name sortKey="Fulton, Ross B" sort="Fulton, Ross B" uniqKey="Fulton R" first="Ross B" last="Fulton">Ross B. Fulton</name><name sortKey="Harty, John T" sort="Harty, John T" uniqKey="Harty J" first="John T" last="Harty">John T. Harty</name><name sortKey="Pham, Nhat Long" sort="Pham, Nhat Long" uniqKey="Pham N" first="Nhat-Long" last="Pham">Nhat-Long Pham</name><name sortKey="Tifrea, Dilea" sort="Tifrea, Dilea" uniqKey="Tifrea D" first="Dilea" last="Tifrea">Dilea Tifrea</name><name sortKey="Varga, Steven M" sort="Varga, Steven M" uniqKey="Varga S" first="Steven M" last="Varga">Steven M. Varga</name></noCountry><country name="États-Unis"><region name="Iowa"><name sortKey="Khanolkar, Aaruni" sort="Khanolkar, Aaruni" uniqKey="Khanolkar A" first="Aaruni" last="Khanolkar">Aaruni Khanolkar</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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