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Regulatory T cells (Tregs) are essential for tolerance to self and environmental Ags, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naive CD4 T cell-DC interactions. In this study, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down but maintain a highly polarized and motile phenotype after recognizing Ag in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or "kinapse." However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking Abs, we show that, whereas CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of Ag. Taken together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals.

Original publication

DOI

10.4049/jimmunol.1401752

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

12/2014

Volume

193

Pages

5894 - 5903

Addresses

Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239; parkerd@ohsu.edu thauland@stanford.edu.

Keywords

Antigen-Presenting Cells, Dendritic Cells, Animals, Mice, Transgenic, Mice, Antigens, CD28, Antigens, CD80, Antigens, Cell Communication, Chemotaxis, Leukocyte, Protein Binding, Female, Male, T-Lymphocytes, Regulatory, Immunological Synapses, Immunomodulation