title: 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.
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.
authors: Melanie P
authors: MP
authors: Matheu
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.
authors: Shivashankar
authors: S
authors: Othy
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.
authors: Milton L
authors: ML
authors: Greenberg
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.
authors: Tobias X
authors: TX
authors: Dong
authors: VIB Inflammation Research Center, University of Ghent, Belgium.
authors: Martijn
authors: M
authors: Schuijs
authors: VIB Inflammation Research Center, University of Ghent, Belgium.
authors: Kim
authors: K
authors: Deswarte
authors: VIB Inflammation Research Center, University of Ghent, Belgium.
authors: Hamida
authors: H
authors: Hammad
authors: VIB Inflammation Research Center, University of Ghent, Belgium.
authors: Bart N
authors: BN
authors: Lambrecht
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.|Department of Neurobiology & Behavior, University of California, Irvine, California, USA.
authors: Ian
authors: I
authors: Parker
authors: Department of Physiology and Biophysics, University of California, Irvine, California, USA.|Institute for Immunology, University of California, Irvine, California, USA.
authors: Michael D
authors: MD
authors: Cahalan
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
chemical_list: D060887:B7 Antigens; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008070:Lipopolysaccharides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
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