Format

Send to

Choose Destination
Sci Immunol. 2017 Jun 2;2(12). pii: eaam6970. doi: 10.1126/sciimmunol.aam6970.

Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection.

Author information

1
Department of Microbiology and Immunology, University of Melbourne, at Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
2
The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne 3000, Australia.
3
World Health Organization Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
4
Department of Microbiology and Immunology, University of Melbourne, at Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia. wakiml@unimelb.edu.au.

Abstract

Nasal epithelial tissue of the upper respiratory tract is the first site of contact by inhaled pathogens such as influenza virus. We show that this region is key to limiting viral spread to the lower respiratory tract and associated disease pathology. Immunization of the upper respiratory tract leads to the formation of local tissue-resident memory CD8+ T cells (Trm cells). Unlike Trm cells in the lung, these cells develop independently of local cognate antigen recognition and transforming growth factor-β signaling and persist with minimal decay, representing a long-term protective population. Repertoire characterization revealed unexpected differences between lung and nasal tissue Trm cells, the composition of which was shaped by the developmental need for lung, but not nasal, Trm cells to recognize antigen within their local tissue. We show that influenza-specific Trm cells in the nasal epithelia can block the transmission of influenza virus from the upper respiratory tract to the lung and, in doing so, prevent the development of severe pulmonary disease. Our findings reveal the protective capacity and longevity of upper respiratory tract Trm cells and highlight the potential of targeting these cells to augment protective responses induced to respiratory viral vaccines.

PMID:
28783656
DOI:
10.1126/sciimmunol.aam6970

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center