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Mol Immunol. 2009 Dec;47(2-3):485-92. doi: 10.1016/j.molimm.2009.08.021. Epub 2009 Sep 20.

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

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Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.


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 tumour 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 CD3epsilon 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.

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