Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
Identifieur interne : 001241 ( Main/Exploration ); précédent : 001240; suivant : 001242Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
Auteurs : Laurel Yong-Hwa Lee [Royaume-Uni] ; Do Lien Anh Ha [Viêt Nam] ; Cameron Simmons [Viêt Nam] ; Menno D. De Jong [Viêt Nam] ; Nguyen Van Vinh Chau [Viêt Nam] ; Reto Schumacher [Royaume-Uni] ; Yan Chun Peng [Royaume-Uni] ; Andrew J. Mcmichael [Royaume-Uni] ; Jeremy J. Farrar [Viêt Nam] ; Geoffrey L. Smith [Royaume-Uni] ; Alain R. M. Townsend [Royaume-Uni] ; Brigitte A. Askonas [Royaume-Uni] ; Sarah Rowland-Jones [Royaume-Uni] ; Tao Dong [Royaume-Uni]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2008.
Abstract
The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza–specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4+ and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8+ T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses.
Url:
DOI: 10.1172/JCI32460
PubMed: 18802496
PubMed Central: 2542885
Affiliations:
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Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Ha, Do Lien Anh" sort="Ha, Do Lien Anh" uniqKey="Ha D" first="Do Lien Anh" last="Ha">Do Lien Anh Ha</name><affiliation wicri:level="1"><nlm:aff id="JCI32460">Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Viêt Nam</country><wicri:regionArea>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea><wicri:noRegion>Ho Chi Minh City</wicri:noRegion></affiliation></author><author><name sortKey="Simmons, Cameron" sort="Simmons, Cameron" uniqKey="Simmons C" first="Cameron" last="Simmons">Cameron Simmons</name><affiliation wicri:level="1"><nlm:aff id="JCI32460">Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Viêt Nam</country><wicri:regionArea>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea><wicri:noRegion>Ho Chi Minh City</wicri:noRegion></affiliation></author><author><name sortKey="De Jong, Menno D" sort="De Jong, Menno D" uniqKey="De Jong M" first="Menno D." last="De Jong">Menno D. De Jong</name><affiliation wicri:level="1"><nlm:aff id="JCI32460">Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Viêt Nam</country><wicri:regionArea>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea><wicri:noRegion>Ho Chi Minh City</wicri:noRegion></affiliation></author><author><name sortKey="Chau, Nguyen Van Vinh" sort="Chau, Nguyen Van Vinh" uniqKey="Chau N" first="Nguyen Van Vinh" last="Chau">Nguyen Van Vinh Chau</name><affiliation wicri:level="1"><nlm:aff id="JCI32460">Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Viêt Nam</country><wicri:regionArea>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea><wicri:noRegion>Ho Chi Minh City</wicri:noRegion></affiliation></author><author><name sortKey="Schumacher, Reto" sort="Schumacher, Reto" uniqKey="Schumacher R" first="Reto" last="Schumacher">Reto Schumacher</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Peng, Yan Chun" sort="Peng, Yan Chun" uniqKey="Peng Y" first="Yan Chun" last="Peng">Yan Chun Peng</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Mcmichael, Andrew J" sort="Mcmichael, Andrew J" uniqKey="Mcmichael A" first="Andrew J." last="Mcmichael">Andrew J. Mcmichael</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Farrar, Jeremy J" sort="Farrar, Jeremy J" uniqKey="Farrar J" first="Jeremy J." last="Farrar">Jeremy J. Farrar</name><affiliation wicri:level="1"><nlm:aff id="JCI32460">Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Viêt Nam</country><wicri:regionArea>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</wicri:regionArea><wicri:noRegion>Ho Chi Minh City</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Geoffrey L" sort="Smith, Geoffrey L" uniqKey="Smith G" first="Geoffrey L." last="Smith">Geoffrey L. Smith</name><affiliation wicri:level="3"><nlm:aff id="JCI32460">Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Department of Virology, Faculty of Medicine, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Townsend, Alain R M" sort="Townsend, Alain R M" uniqKey="Townsend A" first="Alain R. M." last="Townsend">Alain R. M. Townsend</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">Molecular Immunology Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Molecular Immunology Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Askonas, Brigitte A" sort="Askonas, Brigitte A" uniqKey="Askonas B" first="Brigitte A." last="Askonas">Brigitte A. Askonas</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Rowland Jones, Sarah" sort="Rowland Jones, Sarah" uniqKey="Rowland Jones S" first="Sarah" last="Rowland-Jones">Sarah Rowland-Jones</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Dong, Tao" sort="Dong, Tao" uniqKey="Dong T" first="Tao" last="Dong">Tao Dong</name><affiliation wicri:level="4"><nlm:aff id="JCI32460">MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4<sup>+</sup> and CD8<sup>+</sup> memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells isolated from the majority of participants exhibited human influenza–specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4<sup>+</sup> and CD8<sup>+</sup> T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4<sup>+</sup> and CD8<sup>+</sup> T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses.
</p></div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>Viêt Nam</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Oxfordshire</li></region><settlement><li>Londres</li><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Lee, Laurel Yong Hwa" sort="Lee, Laurel Yong Hwa" uniqKey="Lee L" first="Laurel Yong-Hwa" last="Lee">Laurel Yong-Hwa Lee</name></region><name sortKey="Askonas, Brigitte A" sort="Askonas, Brigitte A" uniqKey="Askonas B" first="Brigitte A." last="Askonas">Brigitte A. Askonas</name><name sortKey="Dong, Tao" sort="Dong, Tao" uniqKey="Dong T" first="Tao" last="Dong">Tao Dong</name><name sortKey="Mcmichael, Andrew J" sort="Mcmichael, Andrew J" uniqKey="Mcmichael A" first="Andrew J." last="Mcmichael">Andrew J. Mcmichael</name><name sortKey="Peng, Yan Chun" sort="Peng, Yan Chun" uniqKey="Peng Y" first="Yan Chun" last="Peng">Yan Chun Peng</name><name sortKey="Rowland Jones, Sarah" sort="Rowland Jones, Sarah" uniqKey="Rowland Jones S" first="Sarah" last="Rowland-Jones">Sarah Rowland-Jones</name><name sortKey="Schumacher, Reto" sort="Schumacher, Reto" uniqKey="Schumacher R" first="Reto" last="Schumacher">Reto Schumacher</name><name sortKey="Smith, Geoffrey L" sort="Smith, Geoffrey L" uniqKey="Smith G" first="Geoffrey L." last="Smith">Geoffrey L. Smith</name><name sortKey="Townsend, Alain R M" sort="Townsend, Alain R M" uniqKey="Townsend A" first="Alain R. M." last="Townsend">Alain R. M. Townsend</name></country><country name="Viêt Nam"><noRegion><name sortKey="Ha, Do Lien Anh" sort="Ha, Do Lien Anh" uniqKey="Ha D" first="Do Lien Anh" last="Ha">Do Lien Anh Ha</name></noRegion><name sortKey="Chau, Nguyen Van Vinh" sort="Chau, Nguyen Van Vinh" uniqKey="Chau N" first="Nguyen Van Vinh" last="Chau">Nguyen Van Vinh Chau</name><name sortKey="De Jong, Menno D" sort="De Jong, Menno D" uniqKey="De Jong M" first="Menno D." last="De Jong">Menno D. De Jong</name><name sortKey="Farrar, Jeremy J" sort="Farrar, Jeremy J" uniqKey="Farrar J" first="Jeremy J." last="Farrar">Jeremy J. Farrar</name><name sortKey="Simmons, Cameron" sort="Simmons, Cameron" uniqKey="Simmons C" first="Cameron" last="Simmons">Cameron Simmons</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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