Cited by 982Influenza Virus Research StudiesRespiratory viral infections researchImmune responses and vaccinations

Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans

Wilkinson, Tom M, Li, Chris K F, Chui, Cecilia S C, Huang, Arthur K Y, Perkins, Molly, Liebner, Julia C, Lambkin-Williams, Rob, Gilbert, Anthony +7 more·2012·Nature Medicine

Abstract

Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection. We found a large increase in influenza-specific T cell responses by day 7, when virus was completely cleared from nasal samples and serum antibodies were still undetectable. Preexisting CD4+, but not CD8+, T cells responding to influenza internal proteins were associated with lower virus shedding and less severe illness. These CD4+ cells also responded to pandemic H1N1 (A/CA/07/2009) peptides and showed evidence of cytotoxic activity. These cells are an important statistical correlate of homotypic and heterotypic response and may limit severity of influenza infection by new strains in the absence of specific antibody responses. Our results provide information that may aid the design of future vaccines against emerging influenza strains.

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Crossref · 10.1038/nm.2612

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  • Cross-reactive T cells can provide some degree of protective immunity against respiratory viral infections, as seen in the 2009 influenza H1N1 pandemic.

    “Cross-reactive T cells can provide some degree of protective immunity against respiratory viral infections, as seen in the influenza H1N1 2009 pandemic (Sridhar et al., 2013; Wilkinson et al., 2012).”

    From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Wilkinson et al., 2012

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Authors
Wilkinson, T. M., Li, C. K. F., Chui, C. S. C., Huang, A. K. Y., Perkins, M., Liebner, J. C., Lambkin-Williams, R., Gilbert, A., Oxford, J., Nicholas, B., Staples, K. J., Dong, T., Douek, D. C., McMichael, A. J., & Xu, X.-N.
Affiliations
  • University of Southampton (GB)
  • University of Oxford (GB)
  • National Institutes of Health (US)
Corresponding author
  • Wilkinson, Tom M
  • Xu, Xiao-Ning
Venue
Nature Medicine
Published
2012-01-29
Volume
18
Issue
2
Pages
274-280
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2036182565
Cited by
974
References
43
Citations by year
2026: 23 · 2025: 55 · 2024: 45 · 2023: 77 · 2022: 62 · 2021: 73 · 2020: 79 · 2019: 71 · 2018: 70 · 2017: 59 · 2016: 95 · 2015: 72 · 2014: 69 · 2013: 72 · 2012: 51
FWCI
62.99
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
Funders
  • National Institutes of Health
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
influenza, CD4+ T cells, cytotoxic T lymphocytes, pandemic H1N1, H3N2, H1N1, viral shedding, disease severity, influenza vaccine design
MeSH terms
Adolescent, Adult, Antibodies, Viral, Female, Humans, Immunity, Cellular, Influenza, Human, Male, Middle Aged, Severity of Illness Index, Time Factors, CD4-Positive T-Lymphocytes, Virus Shedding, CD8-Positive T-Lymphocytes, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Young Adult, Immunity, Humoral

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