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

Melanie P. Matheu, Shivashankar Othy, Milton L. Greenberg, Tobias X. Dong, Martijn Schuijs, Kim Deswarte, Hamida Hammad, Bart N. Lambrecht, Ian Parker and Michael D. Cahalan ()
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Melanie P. Matheu: University of California, 285 Irvine Hall, Irvine, California 92697, 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
Kim Deswarte: Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
Hamida Hammad: Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
Bart N. Lambrecht: Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, University of Ghent
Ian Parker: University of California, 285 Irvine Hall, Irvine, California 92697, USA
Michael D. Cahalan: University of California, 285 Irvine Hall, Irvine, California 92697, USA

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7219

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