NDLI: CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation.

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CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation.

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CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dustin, Michael L. Parker, David C. Thauland, Timothy J. Koguchi, Yoshinobu
Description	Author Affiliation: Thauland TJ ( Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239); Koguchi Y ( Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239); Dustin ML ( Department of Pathology, New York University School of Medicine, New York, NY 10016); Parker DC ( Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239)
Abstract	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.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1401752
Journal	The Journal of Immunology
Issue Number	12
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd28 Metabolism Antigens, Cd80 Chemotaxis, Leukocyte Immunology Immunological Synapses T-lymphocytes, Regulatory Animals Antigen-presenting Cells Antigens Cell Communication Dendritic Cells Immunomodulation Mice Mice, Transgenic Protein Binding Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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