Cited by 167Influenza Virus Research StudiesImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection

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Wakim, L M, Smith, J, Caminschi, I, Lahoud, M H, Villadangos, J A·2015·Mucosal Immunology

Abstract

Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the lung. The early stage of infection, while the virus is confined to the lung mucosa, provides the ideal window of opportunity for an effective immune response to control the infection. Tissue-resident memory (Trm) CD8 T cells, located in a variety of tissues including the lung, are ideally situated to act during this window and stall the infection. The factors involved in the differentiation of lung Trm cells remain poorly defined. We demonstrate that recognition of antigen presented locally by dendritic cells (DCs) and transforming growth factor-β (TGFβ) signaling are both required. We exploited this knowledge to develop an antibody-targeted vaccination approach to generate lung Trm cells. Delivering antigen exclusively to respiratory DCs results in the development of lung CD8 Trm cells that are highly protective against lethal influenza challenge. Our results describe an effective vaccination strategy that protects against influenza virus infection.

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  • Insufficient local TGF-β signaling may result in sustained high Eomes expression and an abundance of CD103−CD69+CD8+ Trm cells in the liver.

    “As downregulation of Eomes is required for CD103+CD8+ Trm development via TGF-β signaling32, insufficient local TGF-β signaling may result in sustained high Eomes expression and an abundance of CD103−CD69+CD8+ Trm cells in the liver, consistent with previous reports28,33.”

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Authors
Wakim, L. M., Smith, J., Caminschi, I., Lahoud, M. H., & Villadangos, J. A.
Affiliations
  • The University of Melbourne (AU)
  • Burnet Institute (AU)
Corresponding author
  • Wakim, L M
  • Villadangos, J A
Venue
Mucosal Immunology
Publisher
Elsevier BV
Published
2015-09
Volume
8
Issue
5
Pages
1060-1071
ISSN
1933-0219 (ISSN-L)
OpenAlex
W1994014992
Cited by
167
References
34
Citations by year
2026: 9 · 2025: 13 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 24 · 2020: 14 · 2019: 23 · 2018: 19 · 2017: 8 · 2016: 12 · 2015: 4
FWCI
11.24
Type
journal article
Language
en
Open access
Locations
  • Mucosal Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Melbourne
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
tissue-resident memory T cells, CD8+ T cells, lung dendritic cells, influenza, TGF-beta signaling, antigen presentation, respiratory mucosa, protective immunity
MeSH terms
Animals, Antibodies, Viral, Dendritic Cells, Influenza Vaccines, Lung, Mice, Transgenic, Orthomyxoviridae Infections, Influenza A virus, Vaccination, Mice

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