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.
Allergen exposure functionally alters influenza-specific CD4+ Th1 memory cells in the lung
Disclosures: M. Pepper is on the Vaxart Scientific Advisory Board, but there is no conflict of interest. No other disclosures were reported.
- Award Id(s): U19 A107422,TL1 TR002318,1S10OD024979-01A1
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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