T cell extravasation: demonstration of synergy between activation of CXCR3 and the T cell receptor.
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.
Newton
Peter
P
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
O'Boyle
Graeme
G
Jenkins
Yvonne
Y
Ali
Simi
S
Kirby
John A
JA
D000328:Adult; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D017252:CD3 Complex; D003432:Cross-Linking Reagents; D011948:Receptors, Antigen, T-Cell; D054367:Receptors, CXCR3