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Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios-expressing Foxp3+ regulatory T cells in the lungs
Immunology and Cell Biology ( IF 4 ) Pub Date : 2021-07-12 , DOI: 10.1111/imcb.12492
Chunni Lu 1, 2 , Weisan Chen 1
Affiliation  

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.
更新日期:2021-07-12
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