期刊
JOURNAL OF IMMUNOLOGY
卷 165, 期 6, 页码 3423-3429出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.165.6.3423
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Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. We show that synovial T cells, which are primed CD45RO(+)CD45RB(dull) cells and consequently not expected to express constitutive chemokine receptors, have high levels of the chemokine receptor CXCR4, Sustained expression of CXCR4 was maintained on synovial T cells by specific factors present within the synovial microenvironment, Extensive screening revealed that TGF-beta isoforms induce the expression of CXCR4 on CD4 T cells in vitro. Depletion studies using synovial quid confirmed an important role for TGF-beta1 in the induction of CXCR4 expression in vivo. The only known ligand for CXCR4 is SDF-1, We found SDF-1 on synovial endothelial cells and showed that SDF-1 was able to induce strong integrin-mediated adhesion of synovial fluid T cells to fibronectin and ICAM-1, confirming that CXCR4 expressed on synovial T cells was functional. These results suggest that the persistent induction of CXCR4 on synovial T cells by TGF-beta1 leads to their active, SDF-1-mediated retention in a perivascular distribution within the rheumatoid synovium.
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