Selective lymphocyte chemokine receptor expression in the rheumatoid joint

Objective. In patients with rheumatoid arthritis (RA), chemokines and their receptors are important for lymphocyte trafficking into the inflamed joint . This study was undertaken to characterize the expression of chemokine rec eptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CXCR3, and CX(3)CR1 in normal (N L) peripheral blood (PB), RA PB, and RA synovial fluid (SF). Methods. Using flow Cytometry, immunohistochemistry, and 2-color immunofluo rescence, we defined the expression of chemokine receptors on CD3+ T lympho cytes in RA synovial tissue (ST), RA SF, R-A PB, and NL PB. Results. The percentage of CD3+ lymphocytes expressing CCR2, CCR4, CCR5, an d CX(3)CR1 was significantly elevated in RA PB compared with that in NL PB, while the percentage of CD3+ lymphocytes expressing CCR5 was significantly , enhanced in RA SF compared with that in NL and RA PB. In contrast, simila r percentages of CD3+ lymphocytes in NL PB, RA PB, and RA SF expressed CCR6 and CXCR3. Immunohistochemistry of RA ST showed lymphocyte expression of C CR4, and 2-color immunofluorescence staining revealed RA ST CD3+ lymphocyte s intensely, immunoreactive for CXCR3, suggesting that these 2 receptors ma y be particularly important for CD3+ lymphocyte trafficking to the inflamed joint. In comparisons of chemokine receptor expression on naive (CD45RA+) and memory (CD45RO+) CD3+ lymphocytes, there were greater percentages of me mory CD3+/CD4+ lymphocytes expressing CCR4, CCR5, and CXCR3 than naive CD3/CD4+ lymphocytes in RA PB and RA SF, and greater percentages of memory CD3 +/CD4+ lymphocytes expressing CCR4, CCR5, and CXCR3 than naive CD3+/CD8+ ly mphocytes in RA SF, suggesting receptor up-regulation upon lymphocyte activ ation. In contrast, percentages of CD3+/CD8+ memory lymphocytes expressing CX(3)CR1 were significantly less than percentages of naive CD3+/CD8+ lympho cytes in RA PB, suggesting that this receptor may be down-regulated upon ly mphocyte activation. A major difference between the RA PB and NL PB groups was significantly more CCR4+ memory leukocytes and memory CCR5+/CD3+/CD8+ l ymphocytes in RA PB than NL PB, further suggesting that these receptors may be particularly important for lymphocyte homing to the RA joint. Conclusion. These results identify CCR4, CCR5, CXCR3, and CX(3)CR1 as criti cal chemokine receptors in RA.