Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses

Rachel L. Clement, Joe Daccache, Mostafa T. Mohammed, Alos Diallo, Bruce R. Blazar, Vijay K. Kuchroo, Scott B. Lovitch, Arlene H. Sharpe, Peter T. Sage

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Follicular regulatory T (TFR) cells have specialized roles in modulating follicular helper T (TFH) cell activation of B cells. However, the precise role of TFR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A TFR cell-deleter mouse was developed that selectively deletes TFR cells, facilitating temporal studies. TFR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of TFR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of TFR cells in house dust mite models. TFR cells were found to control TFH13 cell-induced IgE. In vivo, loss of TFR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, TFR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.

Original languageEnglish (US)
Pages (from-to)1360-1371
Number of pages12
JournalNature immunology
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2019

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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    Clement, R. L., Daccache, J., Mohammed, M. T., Diallo, A., Blazar, B. R., Kuchroo, V. K., Lovitch, S. B., Sharpe, A. H., & Sage, P. T. (2019). Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses. Nature immunology, 20(10), 1360-1371. https://doi.org/10.1038/s41590-019-0472-4