F Canete, PabloSweet, RebeccaGonzalez-Figueroa, PaulaPapa, IleniaOhkura, NaganariBolton, HollyRoco Alegre, JonathanCuenca, MartaBassett, KatharineSayin, IsmailBarry, ELopez, Angel F.Canaday, David HMeyer-Hermann, MichaelDoglioni, ClaudioFazekas de St Groth, BarbaraSakaguchi, Shimon, ProfCook, MatthewVinuesa, Carola2020-04-232020-04-230022-1007http://hdl.handle.net/1885/203395Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell–derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell–derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10–producing TF cells but not with total T reg cells, TFR, or IL-10–producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopyThe authors thank Anastasia Wilson and Ann-Maree Hatch for assistance with obtaining tonsil samples and obtaining clinical data; the Australian Cancer Research Foundation Biomolecular Resource Facility and the Imaging and Cytometry Facility (John Curtin School of Medical Research), especially H. Vohra and M. Devoy for FACS sorting and S. Ohms for help with microarray analysis; and B. Kaehler and A. Chua for RNA-seq analysis. C.G. Vinuesa was supported by the Australian National Health and Medical Research Council fellowship (APP1117812), program and project grants (APP1113577), and a Human Frontier Science Program program grant (RGP0033/2015). The authors declare no competing financial interests.application/pdfen-AU© 2019 Cañete et alhttps://creativecommons.org/licenses/by/4.0/201910.1084/jem.201904932023-10-22Creative Commons License (Attribution 4.0 International)