tetano
Editor, Senior Moderator
J Exp Med
. 2023 Nov 6;220(11):e20230112.
doi: 10.1084/jem.20230112. Epub 2023 Sep 12. Allergen exposure functionally alters influenza-specific CD4+ Th1 memory cells in the lung
Mikel J Rüterbusch[SUP] 1 [/SUP], Brian D Hondowicz[SUP] 1 [/SUP], Kennidy K Takehara[SUP] 1 [/SUP], Kurt B Pruner[SUP] 1 [/SUP], Thomas S Griffith[SUP] 2 3 4 5 [/SUP], Marion Pepper[SUP] 1 [/SUP]
Affiliations
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.
. 2023 Nov 6;220(11):e20230112.
doi: 10.1084/jem.20230112. Epub 2023 Sep 12. Allergen exposure functionally alters influenza-specific CD4+ Th1 memory cells in the lung
Mikel J Rüterbusch[SUP] 1 [/SUP], Brian D Hondowicz[SUP] 1 [/SUP], Kennidy K Takehara[SUP] 1 [/SUP], Kurt B Pruner[SUP] 1 [/SUP], Thomas S Griffith[SUP] 2 3 4 5 [/SUP], Marion Pepper[SUP] 1 [/SUP]
Affiliations
- PMID: 37698553
- DOI: 10.1084/jem.20230112
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.