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In vivo anergized T cells form altered immunological synapses in vitro

Academic Article
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Overview

authors

  • Zambricki, E.
  • Zal, T.
  • Yachi, Pia
  • Shigeoka, A.
  • Sprent, Jonathan
  • Gascoigne, Nicholas
  • McKay, Dianne

publication date

  • November 2006

journal

  • American Journal of Transplantation  Journal

abstract

  • T cells contact allogeneic antigen presenting cells (APCs) and assemble, at their contact interface, a molecular platform called the immunological synapse. Synapse-based molecules provide directional signals for the T cell--either positive signals, resulting in T-cell activation, or negative signals causing T-cell inactivation or anergy. To better understand the molecular basis of in vivo T-cell anergy we analyzed the contacts made between in vivo anergized T cells and APCs, and determined which signaling molecules were included or excluded from their immunological synapses. Anergy was induced in TCR transgenic mice by the intravenous injection of semiallogeneic donor spleen cells. T cells from anergized mice were mixed with APCs, the T-cell/APC synapses imaged using deconvolution microscopy, and their molecular compositions were determined. T cells from anergic mice formed unstable immunological synapses in vitro with allogeneic APCs and failed to recruit the signaling proteins necessary to initiate T-cell activation. These findings suggest that T-cell anergy induced by exposure to semiallogeneic donor cells is associated with defects in the earliest events of T-cell activation, immunological synapse formation and recruitment of TCR-mediated signaling proteins.

subject areas

  • Animals
  • Antigen-Presenting Cells
  • Antigens, CD8
  • Clonal Anergy
  • Gap Junctions
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • Transplantation, Homologous
  • Transplantation, Isogeneic
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Research

keywords

  • T cells
  • alloantigen
  • anergy
  • antigen presenting cells
  • signaling
  • synapses
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Identity

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2006.01517.x

PubMed ID

  • 16952297
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Additional Document Info

start page

  • 2572

end page

  • 2579

volume

  • 6

issue

  • 11

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