A distinct subpopulation of CD25^sup -^ T-follicular regulatory cells localizes in the germinal centers

T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differenti...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 114; no. 31; p. E6400
Main Authors Wing, James Badger, Kitagawa, Yohko, Locci, Michela, Hume, Hannah, Tay, Christopher, Morita, Takayoshi, Kidani, Yujiro, Matsuda, Kyoko, Inoue, Takeshi, Kurosaki, Tomohiro, Crotty, Shane, Coban, Cevayir, Ohkura, Naganari, Sakaguchi, Shimon
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences 01.08.2017
Subjects
CD25 antigen
Cell differentiation
Cell survival
Cells
CXCR5 protein
Differentiation (biology)
Effector cells
Foxp3 protein
Genes
Germinal centers
Immunoregulation
Interleukin 2
Lymphocytes B
Lymphocytes T
Molecules
PD-1 protein
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Summary:T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differentiation is inhibited by IL-2, regulatory T (Treg) cell differentiation and survival depend on it. Here, we describe a CD25- subpopulation within both murine and human PD1+CXCR5+Foxp3+ Tfr cells. It is preferentially located in the GC and can be clearly differentiated from CD25+ non-GC-Tfr, Tfh, and effector Treg (eTreg) cells by the expression of a wide range of molecules. In comparison to CD25+ Tfr and eTreg cells, CD25- Tfr cells partially down-regulate IL-2-dependent canonical Treg features, but retain suppressive function, while simultaneously up-regulating genes associated with Tfh and GC-Tfh cells. We suggest that, similar to Tfh cells, Tfr cells follow a differentiation pathway generating a mature GC-localized subpopulation, CD25- Tfr cells.
ISSN:0027-8424
1091-6490