CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells can be altered by environmental antigens and cytokines released during heterologous, antigen-independent immune responses is currently unclear. We therefore investigated how influenza-specific CD4+ Th1 TRM in the lung are impacted by a subsequent Th2-inducing respiratory house dust mite (HDM) exposure. Although naïve influenza-specific CD4+ T cells in the lymph nodes do not respond to HDM, influenza-specific CD4+ TRM in the lungs do respond to a subsequent allergen exposure by decreasing expression of the transcription factor T-bet. This functional alteration is associated with decreased IFN-γ production upon restimulation and improved disease outcomes following heterosubtypic influenza challenge. Further investigation revealed that ST2 signaling in CD4+ T cells during allergic challenge is necessary to induce these changes in lung-resident influenza-specific CD4+ TRM. Thus, heterologous antigen exposure or ST2-signaling can drive persistent changes in CD4+ Th1 TRM populations and impact protection upon reinfection.
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September 12 2023
Allergen exposure functionally alters influenza-specific CD4+ Th1 memory cells in the lung
Mikel J. Rüterbusch
,
Mikel J. Rüterbusch
(Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
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Brian D. Hondowicz
,
Brian D. Hondowicz
(Conceptualization, Methodology)
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
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Kennidy K. Takehara
,
Kennidy K. Takehara
(Investigation, Resources)
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
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Kurt B. Pruner
,
Kurt B. Pruner
(Investigation, Methodology)
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
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Thomas S. Griffith
,
Thomas S. Griffith
(Resources, Writing - review & editing)
2Department of Urology,
University of Minnesota
, Minneapolis, MN, USA
3
Microbiology, Immunology, and Cancer Biology Ph.D. Program, University of Minnesota
, Minneapolis, MN, USA
4
Center for Immunology, University of Minnesota
, Minneapolis, MN, USA
5
Masonic Cancer Center, University of Minnesota
, Minneapolis, MN, USA
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Marion Pepper
(Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
Correspondence to Marion Pepper: mpepper@uw.edu
Search for other works by this author on:
Mikel J. Rüterbusch
Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
Brian D. Hondowicz
Conceptualization, Methodology
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
Kennidy K. Takehara
Investigation, Resources
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
Kurt B. Pruner
Investigation, Methodology
1Department of Immunology,
School of Medicine, University of Washington
, Seattle, WA, USA
Thomas S. Griffith
Resources, Writing - review & editing
2Department of Urology,
University of Minnesota
, Minneapolis, MN, USA
3
Microbiology, Immunology, and Cancer Biology Ph.D. Program, University of Minnesota
, Minneapolis, MN, USA
4
Center for Immunology, University of Minnesota
, Minneapolis, MN, USA
5
Masonic Cancer Center, University of Minnesota
, Minneapolis, MN, USA
Correspondence to Marion Pepper: mpepper@uw.edu
Disclosures: M. Pepper is on the Vaxart Scientific Advisory Board, but there is no conflict of interest. No other disclosures were reported.
Received:
January 17 2023
Revision Received:
July 11 2023
Accepted:
August 22 2023
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
National Institutes of Health
- Award Id(s): U19 A107422,TL1 TR002318,1S10OD024979-01A1
© 2023 Rüterbusch et al.
2023
Rüterbusch et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2023) 220 (11): e20230112.
Article history
Received:
January 17 2023
Revision Received:
July 11 2023
Accepted:
August 22 2023
Citation
Mikel J. Rüterbusch, Brian D. Hondowicz, Kennidy K. Takehara, Kurt B. Pruner, Thomas S. Griffith, Marion Pepper; Allergen exposure functionally alters influenza-specific CD4+ Th1 memory cells in the lung. J Exp Med 6 November 2023; 220 (11): e20230112. doi: https://doi.org/10.1084/jem.20230112
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