UMMS Affiliation

Department of Pathology

Publication Date

2019-08-14

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunopathology | Pathological Conditions, Signs and Symptoms | Pathology | Virus Diseases

Abstract

Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.

Keywords

Memory T cells, T helper cells, Influenza A virus, Inflammation, NK cells, Respiratory infections, Cytokines, T cells

Rights and Permissions

Copyright: © 2019 McKinstry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.1371/journal.ppat.1007989

Source

PLoS Pathog. 2019 Aug 14;15(8):e1007989. doi: 10.1371/journal.ppat.1007989. eCollection 2019 Aug. Link to article on publisher's site

Journal/Book/Conference Title

PLoS pathogens

Related Resources

Link to Article in PubMed

PubMed ID

31412088

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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