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Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming

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  • Melanie P. Matheu

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA
    Present address: University of California San Francisco Diabetes Center, UCSF, California, USA)

  • Shivashankar Othy

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA)

  • Milton L. Greenberg

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA)

  • Tobias X. Dong

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA)

  • Martijn Schuijs

    (Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
    ErasmusMC)

  • Kim Deswarte

    (Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
    ErasmusMC)

  • Hamida Hammad

    (Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
    ErasmusMC)

  • Bart N. Lambrecht

    (Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
    ErasmusMC)

  • Ian Parker

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA
    University of California, McGaugh Hall, Irvine, California 92697, USA)

  • Michael D. Cahalan

    (University of California, 285 Irvine Hall, Irvine, California 92697, USA
    Institute for Immunology, University of California, 285 Irvine Hall, Irvine, California 92697, USA)

Abstract

Foxp3+ regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC:Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg–Tconv interaction times, increases the volume of DC:Tconv clusters and enhances subsequent Tconv proliferation in vivo. Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming.

Suggested Citation

  • Melanie P. Matheu & Shivashankar Othy & Milton L. Greenberg & Tobias X. Dong & Martijn Schuijs & Kim Deswarte & Hamida Hammad & Bart N. Lambrecht & Ian Parker & Michael D. Cahalan, 2015. "Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7219
    DOI: 10.1038/ncomms7219
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