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Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
Laurel Yong-Hwa Lee, … , Sarah Rowland-Jones, Tao Dong
Laurel Yong-Hwa Lee, … , Sarah Rowland-Jones, Tao Dong
Published September 18, 2008
Citation Information: J Clin Invest. 2008;118(10):3478-3490. https://doi.org/10.1172/JCI32460.
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Research Article Article has an altmetric score of 11

Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

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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.

Authors

Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, Menno D. de Jong, Nguyen Van Vinh Chau, Reto Schumacher, Yan Chun Peng, Andrew J. McMichael, Jeremy J. Farrar, Geoffrey L. Smith, Alain R.M. Townsend, Brigitte A. Askonas, Sarah Rowland-Jones, Tao Dong

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Figure 5

Effector functions displayed by CD4+ and CD8+ T cell clones upon recognition of target cells infected with the rVACVs expressing H5N1 M1 or NP.

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Effector functions displayed by CD4+ and CD8+ T cell clones upon recogni...
Representative examples. (A and C) 51Cr release assay. Cross-reactive cytolytic activities against target cells infected with H5N1 NP-VACV (A) or H5N1 M1-VACV (C) displayed by CD8+ T cell clones specific for NP 258–273 (donor HUK21) (A) or for M1 58–66 (donor HUK01) (B). E:T, effector to target ratio. (B and D) ICS for effector cytokine secretion or upregulation of degranulation marker by CD8+ T cell clones specific for NP 258–273 (donor HUK21) (B) or for M1 58–66 (donor HUK01) (D) in recognition of peptide-pulsed or VACV-infected target cells. (E and F) ICS for effector cytokine secretion by CD4+ T cell clones specific for M1 241–252 (donor HUK01) (E) or for M1 95–112 (donor HUK21) (F).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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