title: FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability.
abstract: Here, we test the role of FoxP3(+) regulatory T cells (Tregs) in controlling T follicular helper (Tfh) and germinal centre (GC) B-cell responses to influenza. In contrast to the idea that Tregs suppress T-cell responses, we find that Treg depletion severely reduces the Tfh cell response to influenza virus. Furthermore, Treg depletion prevents the accumulation of influenza-specific GCs. These effects are not due to alterations in TGFβ availability or a precursor-progeny relationship between Tregs and Tfh cells, but are instead mediated by increased availability of IL-2, which suppresses the differentiation of Tfh cells and as a consequence, compromises the GC B response. Thus, Tregs promote influenza-specific GC responses by preventing excessive IL-2 signalling, which suppresses Tfh cell differentiation.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: León
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Bradley
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: André
authors.initials: A
authors.lastname: Ballesteros-Tato
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2