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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms7219

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

Journal article published in 2015 by Melanie P. Matheu, Shivashankar Othy ORCID, Milton L. Greenberg, Tobias X. Dong, Martijn Schuijs, Kim Deswarte ORCID, Hamida Hammad ORCID, Bart N. Lambrecht, Ian Parker, Michael D. Cahalan
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.