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


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.

SUBMITTER: Matheu MP 

PROVIDER: S-EPMC4347855 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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

Matheu Melanie P MP   Othy Shivashankar S   Greenberg Milton L ML   Dong Tobias X TX   Schuijs Martijn M   Deswarte Kim K   Hammad Hamida H   Lambrecht Bart N BN   Parker Ian I   Cahalan Michael D MD  

Nature communications 20150205


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 im  ...[more]

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