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

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  • Ana Raquel Maceiras

    (Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
    Instituto Gulbenkian de Ciência)

  • Silvia Cristina Paiva Almeida

    (Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
    Instituto Gulbenkian de Ciência)

  • Encarnita Mariotti-Ferrandiz

    (Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    AP-HP, Hôpital Pitié-Salpêtrière)

  • Wahiba Chaara

    (Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    AP-HP, Hôpital Pitié-Salpêtrière)

  • Fadi Jebbawi

    (INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3))

  • Adrien Six

    (Sorbonne Universités, UPMC Univ Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    AP-HP, Hôpital Pitié-Salpêtrière)

  • 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)
    INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (i3)
    AP-HP, Hôpital Pitié-Salpêtrière)

  • Jose Faro

    (Instituto Gulbenkian de Ciência
    Área de Immunoloxía, Facultade de Bioloxía, Universidade de Vigo
    Centro de Investigacións Biomédicas (CINBIO), Universidade de Vigo
    Instituto Biomédico de Vigo)

  • Luis Graca

    (Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
    Instituto Gulbenkian de Ciência)

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.

Suggested Citation

  • Ana Raquel Maceiras & Silvia Cristina Paiva Almeida & Encarnita Mariotti-Ferrandiz & Wahiba Chaara & Fadi Jebbawi & Adrien Six & Shohei Hori & David Klatzmann & Jose Faro & Luis Graca, 2017. "T follicular helper and T follicular regulatory cells have different TCR specificity," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15067
    DOI: 10.1038/ncomms15067
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