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Nat Commun. 2017 Apr 21;8:15067. doi: 10.1038/ncomms15067.

T follicular helper and T follicular regulatory cells have different TCR specificity.

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
2
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
3
Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), F-75005 Paris, France.
4
INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), F-75005 Paris, France.
5
AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), F-75651 Paris, France.
6
Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
7
Área de Immunoloxía, Facultade de Bioloxía, Universidade de Vigo, 36310 Vigo, Spain.
8
Centro de Investigacións Biomédicas (CINBIO), Universidade de Vigo, 36310 Vigo, Spain.
9
Instituto Biomédico de Vigo, 36310 Vigo, Spain.

Abstract

Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity.

PMID:
28429709
PMCID:
PMC5413949
DOI:
10.1038/ncomms15067
[Indexed for MEDLINE]
Free PMC Article

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