tetano
Editor, Senior Moderator
Immunol Cell Biol
. 2021 Jul 12.
doi: 10.1111/imcb.12492. Online ahead of print.
Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios-expressing Foxp3 [SUP]+[/SUP] regulatory T cells in the lungs
Chunni Lu[SUP] 1 2 [/SUP], Weisan Chen[SUP] 1 [/SUP]
Affiliations
Abstract
Foxp3[SUP]+[/SUP] regulatory T cells (Tregs) represent a special lineage of CD4[SUP]+[/SUP] 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, we track Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] and Foxp3[SUP]+[/SUP] Helios[SUP]-[/SUP] Tregs in the lungs, mLNs and spleens of influenza virus-infected and uninfected control mice. Our data show that while there is a co-existence of Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] and Foxp3[SUP]+[/SUP] Helios[SUP]-[/SUP] 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[SUP]+[/SUP] Helios[SUP]+[/SUP] cells. We further demonstrate that, after the clearance of primary infection, Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] cells have the ability to persist in the tissues over their Helios[SUP]-[/SUP] counterparts. More importantly, Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs accumulated in an accelerated kinetics during recall response to reinfection. In vitro analysis of Treg suppressive function reveals that Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs are more capable of suppressing influenza virus-specific CD8[SUP]+[/SUP] T cell activation, cytokine production and proliferation. Together, our data provide new insights into Treg responses during primary and secondary influenza virus infection and suggest that it is Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs that predominantly drive the Treg responses.
Keywords: Accumulation; Helios; Influenza virus; Persistence; Regulatory T cells.
. 2021 Jul 12.
doi: 10.1111/imcb.12492. Online ahead of print.
Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios-expressing Foxp3 [SUP]+[/SUP] regulatory T cells in the lungs
Chunni Lu[SUP] 1 2 [/SUP], Weisan Chen[SUP] 1 [/SUP]
Affiliations
- PMID: 34251701
- DOI: 10.1111/imcb.12492
Abstract
Foxp3[SUP]+[/SUP] regulatory T cells (Tregs) represent a special lineage of CD4[SUP]+[/SUP] 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, we track Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] and Foxp3[SUP]+[/SUP] Helios[SUP]-[/SUP] Tregs in the lungs, mLNs and spleens of influenza virus-infected and uninfected control mice. Our data show that while there is a co-existence of Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] and Foxp3[SUP]+[/SUP] Helios[SUP]-[/SUP] 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[SUP]+[/SUP] Helios[SUP]+[/SUP] cells. We further demonstrate that, after the clearance of primary infection, Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] cells have the ability to persist in the tissues over their Helios[SUP]-[/SUP] counterparts. More importantly, Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs accumulated in an accelerated kinetics during recall response to reinfection. In vitro analysis of Treg suppressive function reveals that Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs are more capable of suppressing influenza virus-specific CD8[SUP]+[/SUP] T cell activation, cytokine production and proliferation. Together, our data provide new insights into Treg responses during primary and secondary influenza virus infection and suggest that it is Foxp3[SUP]+[/SUP] Helios[SUP]+[/SUP] Tregs that predominantly drive the Treg responses.
Keywords: Accumulation; Helios; Influenza virus; Persistence; Regulatory T cells.