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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B7 Antigens / genetics
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B7 Antigens / immunology
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CTLA-4 Antigen / genetics
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CTLA-4 Antigen / immunology*
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Cell Communication / drug effects
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Cell Proliferation
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Crosses, Genetic
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Dendritic Cells / cytology*
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Female
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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Gene Expression
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Genes, Reporter
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / immunology
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Lipopolysaccharides / pharmacology
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Lymph Nodes / cytology*
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Lymph Nodes / immunology
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Lymphocyte Activation
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Male
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Mice
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Mice, Transgenic
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Microscopy, Fluorescence, Multiphoton
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Signal Transduction
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T-Lymphocytes, Regulatory / cytology*
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T-Lymphocytes, Regulatory / immunology
Substances
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B7 Antigens
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CTLA-4 Antigen
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Lipopolysaccharides
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enhanced green fluorescent protein
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Green Fluorescent Proteins