Selective accumulation of CCR5+ T lymphocytes into inflamed joints of rheumatoid arthritis

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Abstract
Chemokines and their receptors play critical roles in the selective recruitment of various subsets of leukocytes. Recent studies have indicated that some chemokine receptors are differentially expressed on Th1 and Th2 cells. However, available data concerning the presence of T cells with a Th1 or a Th2 character and the expression of chemokine receptors on infiltrating T cells in the rheumatic joint are still limited. In this study, we investigated the expression of CC chemokine receptor 4 (CCR4) and CCR5, which have been shown to be preferentially expressed on Th2 and Th1 respectively on T cells from rheumatoid arthritis (RA) patients. Although both CCR5+ and CCR4+ CD4+ T cell populations were observed in peripheral blood mononuclear cells from healthy controls and osteoarthritis patients, these cell populations were decreased in patients with active RA. In contrast, the vast majority of synovial fluid (SF) T cells from active RA patients expressed CCR5 but not CCR4. CCR5 ligands, MIP-1α and RANTES, were found in RA SF at high levels. CCR5+ CD4+ T cells from SF mononuclear cells of RA patients produced IFN-γ but not IL-4 in response to anti-CD3 stimulation in vitro. These results indicated that differential expression of chemokine receptors plays a critical role for selective recruitment of pro-inflammatory T cells into the joints of RA.