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

Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans
Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans
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.
1078-8956
274-280
Wilkinson, Tom M.A.
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Li, Chris K.F
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Chui, Cecilia S.C.
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Huang, Arthur K.Y.
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Perkins, Molly
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Liebner, Julia C.
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Lambkin-Williams, Rob
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Gilbert, Anthony
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Oxford, John
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Nicholas, Ben
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Staples, Karl J.
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Dong, Tao
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Douek, Daniel C.
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McMichael, Andrew J
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Xu, Xiao-Ning
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Wilkinson, Tom M.A.
8c55ebbb-e547-445c-95a1-c8bed02dd652
Li, Chris K.F
3a4b0c26-5938-4909-b560-c28435683339
Chui, Cecilia S.C.
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Huang, Arthur K.Y.
2f16b9a4-b21f-4d13-a998-69ab802ecf16
Perkins, Molly
d877959b-ea86-4808-b973-cdaf01660b26
Liebner, Julia C.
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Lambkin-Williams, Rob
1a3f0888-ffa4-400c-a65f-9232fb56dd40
Gilbert, Anthony
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Oxford, John
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Nicholas, Ben
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Staples, Karl J.
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Dong, Tao
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Douek, Daniel C.
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McMichael, Andrew J
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Xu, Xiao-Ning
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Wilkinson, Tom M.A., Li, Chris K.F, Chui, Cecilia S.C., Huang, Arthur K.Y., Perkins, Molly, Liebner, Julia C., Lambkin-Williams, Rob, Gilbert, Anthony, Oxford, John, Nicholas, Ben, Staples, Karl J., Dong, Tao, Douek, Daniel C., McMichael, Andrew J and Xu, Xiao-Ning (2012) Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nature Medicine, 18 (2), 274-280. (doi:10.1038/nm.2612). (PMID:22286307)

Record type: Article

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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More information

Published date: 29 January 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 341372
URI: http://eprints.soton.ac.uk/id/eprint/341372
ISSN: 1078-8956
PURE UUID: 961775e5-1838-4e1b-81e6-a69546e3a025
ORCID for Ben Nicholas: ORCID iD orcid.org/0000-0003-1467-9643
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

Catalogue record

Date deposited: 23 Jul 2012 14:09
Last modified: 15 Mar 2024 03:27

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Contributors

Author: Chris K.F Li
Author: Cecilia S.C. Chui
Author: Arthur K.Y. Huang
Author: Molly Perkins
Author: Julia C. Liebner
Author: Rob Lambkin-Williams
Author: Anthony Gilbert
Author: John Oxford
Author: Ben Nicholas ORCID iD
Author: Karl J. Staples ORCID iD
Author: Tao Dong
Author: Daniel C. Douek
Author: Andrew J McMichael
Author: Xiao-Ning Xu

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