Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios‐expressing Foxp3+ regulatory T cells in the lungs. Issue 10 (15th August 2021)

• Record Type: Journal Article
• Authors: Lu, Chunni; Chen, Weisan
• Is Part Of: Immunology and cell biology. Volume 99:Issue 10(2021)
• Page Start: 1011
• Page End: 1025
• Publication Date: 2021-08-15
• Subjects: accumulation -- Helios -- influenza virus -- persistence -- regulatory T cells; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12492
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: Foxp3 + regulatory T cells (Tregs) represent a special lineage of CD4 + T cells. Analysis of Treg response during primary and secondary influenza virus infection clearly demonstrates a robust accumulation of Tregs into the infected lungs and the existence of a population of long‐lived antigen‐specific memory Tregs in the same tissues after resolution of the infection. However, it remains unknown whether these Tregs co‐express Helios, a member of the Ikaros transcription factor family. In this study, Foxp3 + Helios + and Foxp3 + Helios ‐ Tregs in the lungs, mLNs and spleens of influenza virus‐infected and uninfected control mice were tracked. The data show that while there is a co‐existence of Foxp3 + Helios + and Foxp3 + Helios ‐ Tregs in the tissues, the accumulated Tregs in the lungs and lung‐draining mediastinal lymph nodes (mLNs) of the infected mice are highly enriched for Foxp3 + Helios + cells. It was further demonstrated that, after the clearance of primary infection, Foxp3 + Helios + cells have the ability to persist in the tissues over their Helios ‐ counterparts. More importantly, Foxp3 + Helios + Tregs accumulated in an accelerated kinetics during recall response to reinfection. In vitro analysis of Treg suppressive function revealed that Foxp3 + Helios + Tregs are more capable of suppressing influenza virus‐specific CD8 + T cell activation, cytokine production and proliferation. Together, the data provide new insights into Treg responses during primary and secondary influenza virus infection and suggest that Foxp3 + Helios + Tregs predominantly drive the Treg responses. Abstract : In this study, we showed that, after intranasal influenza infection, Tregs in the lungs and lung‐draining mediastinal lymph nodes (mLNs) of infected mice are highly enriched with Foxp3 + Helios + cells. These cells persist in the lung and are more responsive in reinfection.