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M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

Eliasson, D. G. ; Omokanye, A. ; Schön, K. ; Wenzel, U. A. ; Bernasconi, V. ; Bemark, M. LU orcid ; Kolpe, A. ; El Bakkouri, K. ; Ysenbaert, T. and Deng, L. , et al. (2018) In Mucosal Immunology 11(1). p.273-289
Abstract

Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A d restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A mice were significantly less well protected compared with... (More)

Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A d restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2 b) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69 + CD103 low M2e-specific memory CD4 T cells were αβ TCR + and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.

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publishing date
type
Contribution to journal
publication status
published
in
Mucosal Immunology
volume
11
issue
1
pages
273 - 289
publisher
Nature Publishing Group
external identifiers
  • pmid:28295019
  • scopus:85038869067
ISSN
1933-0219
DOI
10.1038/mi.2017.14
language
English
LU publication?
no
id
2df5ed21-5d56-4f41-a6c2-45c565b1b59b
date added to LUP
2023-12-06 17:08:44
date last changed
2024-08-09 21:51:26
@article{2df5ed21-5d56-4f41-a6c2-45c565b1b59b,
  abstract     = {{<p>Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A d restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2 b) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69 + CD103 low M2e-specific memory CD4 T cells were αβ TCR + and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.</p>}},
  author       = {{Eliasson, D. G. and Omokanye, A. and Schön, K. and Wenzel, U. A. and Bernasconi, V. and Bemark, M. and Kolpe, A. and El Bakkouri, K. and Ysenbaert, T. and Deng, L. and Fiers, W. and Saelens, X. and Lycke, N.}},
  issn         = {{1933-0219}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{273--289}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Mucosal Immunology}},
  title        = {{M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection}},
  url          = {{http://dx.doi.org/10.1038/mi.2017.14}},
  doi          = {{10.1038/mi.2017.14}},
  volume       = {{11}},
  year         = {{2018}},
}