T cell responses to whole SARS coronavirus in humans.
Identifieur interne : 002F99 ( Main/Curation ); précédent : 002F98; suivant : 003000T cell responses to whole SARS coronavirus in humans.
Auteurs : Chris Ka-Fai Li [Royaume-Uni] ; Hao Wu ; Huiping Yan ; Shiwu Ma ; Lili Wang ; Mingxia Zhang ; Xiaoping Tang ; Nigel J. Temperton ; Robin A. Weiss ; Jason M. Brenchley ; Daniel C. Douek ; Juthathip Mongkolsapaya ; Bac-Hai Tran ; Chen-Lung Steve Lin ; Gavin R. Screaton ; Jin-Lin Hou ; Andrew J. Mcmichael ; Xiao-Ning XuSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2008.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Anticorps antiviraux (immunologie), Cytokines (immunologie), Femelle, Humains, Lymphocytes T CD8+ (immunologie), Lymphocytes auxiliaires Th2 (immunologie), Mâle, Mémoire immunologique, Protéine de membrane-1 associée au lysosome (immunologie), Protéome (immunologie), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (mortalité), Vaccins antiviraux (immunologie), Virus du SRAS (immunologie), Études de cohortes.
- MESH :
- immunologie : Anticorps antiviraux, Cytokines, Lymphocytes T CD8+, Lymphocytes auxiliaires Th2, Protéine de membrane-1 associée au lysosome, Protéome, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Virus du SRAS.
- mortalité : Syndrome respiratoire aigu sévère.
- Adulte, Adulte d'âge moyen, Femelle, Humains, Mâle, Mémoire immunologique, Études de cohortes.
English descriptors
- KwdEn :
- Adult, Antibodies, Viral (immunology), CD8-Positive T-Lymphocytes (immunology), Cohort Studies, Cytokines (immunology), Female, Humans, Immunologic Memory, Leukocyte Common Antigens (immunology), Lysosomal-Associated Membrane Protein 1 (immunology), Male, Middle Aged, Proteome (immunology), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (mortality), Th2 Cells (immunology), Tumor Necrosis Factor Receptor Superfamily, Member 7 (immunology), Viral Vaccines (immunology).
- MESH :
- chemical , immunology : Antibodies, Viral, Cytokines, Leukocyte Common Antigens, Lysosomal-Associated Membrane Protein 1, Proteome, Tumor Necrosis Factor Receptor Superfamily, Member 7, Viral Vaccines.
- immunology : CD8-Positive T-Lymphocytes, SARS Virus, Severe Acute Respiratory Syndrome, Th2 Cells.
- mortality : Severe Acute Respiratory Syndrome.
- Adult, Cohort Studies, Female, Humans, Immunologic Memory, Male, Middle Aged.
Abstract
Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.
DOI: 10.4049/jimmunol.181.8.5490
PubMed: 18832706
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pubmed:18832706Le document en format XML
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<term>Antibodies, Viral (immunology)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Cohort Studies</term>
<term>Cytokines (immunology)</term>
<term>Female</term>
<term>Humans</term>
<term>Immunologic Memory</term>
<term>Leukocyte Common Antigens (immunology)</term>
<term>Lysosomal-Associated Membrane Protein 1 (immunology)</term>
<term>Male</term>
<term>Middle Aged</term>
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<term>Severe Acute Respiratory Syndrome (mortality)</term>
<term>Th2 Cells (immunology)</term>
<term>Tumor Necrosis Factor Receptor Superfamily, Member 7 (immunology)</term>
<term>Viral Vaccines (immunology)</term>
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<term>Adulte d'âge moyen</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Cytokines (immunologie)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes auxiliaires Th2 (immunologie)</term>
<term>Mâle</term>
<term>Mémoire immunologique</term>
<term>Protéine de membrane-1 associée au lysosome (immunologie)</term>
<term>Protéome (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (mortalité)</term>
<term>Vaccins antiviraux (immunologie)</term>
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<term>Études de cohortes</term>
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<term>Cytokines</term>
<term>Leukocyte Common Antigens</term>
<term>Lysosomal-Associated Membrane Protein 1</term>
<term>Proteome</term>
<term>Tumor Necrosis Factor Receptor Superfamily, Member 7</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Cytokines</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphocytes auxiliaires Th2</term>
<term>Protéine de membrane-1 associée au lysosome</term>
<term>Protéome</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vaccins antiviraux</term>
<term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Th2 Cells</term>
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<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>
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<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Immunologic Memory</term>
<term>Male</term>
<term>Middle Aged</term>
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<term>Adulte d'âge moyen</term>
<term>Femelle</term>
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<term>Mâle</term>
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<front><div type="abstract" xml:lang="en">Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.</div>
</front>
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