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T cell extravasation: Demonstration of synergy between activation of CXCR3 and the T cell receptor

Lookup NU author(s): Dr Graeme O'Boyle, Professor Simi Ali, Professor John Kirby

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Abstract

Endothelial cells present chemokines to T cells and can also stimulate the T cell antigen receptor by presentation of peptide-MHC antigen complexes. This study was designed to investigate the potential synergy between stimulation of the chemokine receptor CXCR3 and the human T cell receptor complex. Transendothelial T cell migration towards CXCL10 was modified by crosslinking CD3 immediately before addition to the endothelium. When resting endothelium was used, T cells which had been activated by crosslinking CD3 for only 1 min showed a significant reduction (p < 0.0001) in migration when compared with untreated T cells. By contrast, endothelial cells which had been activated by stimulation with interferon-gamma and turnout necrosis factor-alpha supported a specific increase in the migration of activated T cells; this was most apparent after CD3 had been activated for 90 min (p < 0.0001). The molecular basis for synergy between CXCR3 and the T cell receptor complex was investigated by measurement of fluorescence resonance energy transfer. This showed that CXCL10 induced a close (<10 nm) spatial association between CXCR3 and the CD3 epsilon subunit on the cell-surface. These data demonstrate that stimulation of both CXCR3 and the T cell receptor has the potential to enhance specifically both the proliferation and extravasation of specific T cells during episodes of local inflammation. (C) 2009 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Newton P, O'Boyle G, Jenkins Y, Ali S, Kirby JA

Publication type: Article

Publication status: Published

Journal: Molecular Immunology

Year: 2009

Volume: 47

Issue: 2-3

Pages: 485-492

Date deposited: 19/03/2010

ISSN (print): 0161-5890

ISSN (electronic): 1872-9142

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.molimm.2009.08.021

DOI: 10.1016/j.molimm.2009.08.021


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