Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice

Hao Wu, Yuxin Chen, Hong Liu, Lin Lin Xu, Paula Teuscher, Shixia Wang, Shan Lu, Alexander L. Dent

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr-cell function in the GC is not well understood. Here, we define Tfr cells as a CD4+ Foxp3+ CXCR5hi PD-1hi CD25low TIGIThigh T-cell population. Furthermore, we have used a novel mouse model ("Bcl6FC") to delete the Bcl6 gene in Foxp3+ T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh- and GCB-cell populations. However, Bcl6FC mice produce altered antigen-specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV-1 gp120 "prime-boost" vaccine model. In an autoimmune lupus model, we observed strongly elevated anti-DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon-γ, IL-10 and IL-21. Loss of Tfr cells therefore leads to highly abnormal Tfh-cell and GCB-cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response.

Original languageEnglish (US)
Pages (from-to)1152-1161
Number of pages10
JournalEuropean Journal of Immunology
Volume46
Issue number5
DOIs
StatePublished - May 1 2016

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Keywords

  • Antibody
  • Bcl6
  • Follicular T cells
  • Germinal Center Response
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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