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J Exp Med. 2019 Aug 5;216(8):1843-1856. doi: 10.1084/jem.20190493. Epub 2019 Jun 17.

Regulatory roles of IL-10-producing human follicular T cells.

Author information

1
Department of Immunology and Infectious Disease and Centre for Personalised Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
2
Laboratory of Experimental Immunology, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka, Japan.
3
Discipline of Pathology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, New South Wales, Australia.
4
Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH.
5
Cytokine Receptor Laboratory, Centre for Cancer Biology, Adelaide, Australia.
6
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
7
Department Pathology, San Raffaele Scientific Institute, Università Vita-Salute, Milan, Italy.
8
Department of Immunology, Canberra Hospital, Canberra, Australia.
9
Department of Immunology and Infectious Disease and Centre for Personalised Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia carola.vinuesa@anu.edu.au.

Abstract

Mucosal 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 atopy.

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