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

Ana Raquel Maceiras, Silvia Cristina Paiva Almeida, Encarnita Mariotti-Ferrandiz, Wahiba Chaara, Fadi Jebbawi, Adrien Six, Shohei Hori, David Klatzmann, Jose Faro and Luis Graca ()
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Ana Raquel Maceiras: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
Silvia Cristina Paiva Almeida: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
Encarnita Mariotti-Ferrandiz: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
Wahiba Chaara: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
Fadi Jebbawi: INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
Adrien Six: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
Shohei Hori: Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences
David Klatzmann: Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
Jose Faro: Instituto Gulbenkian de Ciência
Luis Graca: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15067

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