Chemokine receptor CCR4 on CD4(+) T cells in juvenile rheumatoid arthritissynovial fluid defines a subset of cells with increased IL-4 : IFN-gamma mRNA ratios

To understand the mechanisms that promote recruitment and survival of T cel ls within the pediatric inflamed joint, we have studied the expression of C CR4 and CCR5 on synovial fluid T cells and matched peripheral blood samples from juvenile rheumatoid arthritis (JRA) patients using three-color flow c ytometric analysis. Thymus- and activation-regulated chemokine and macropha ge-derived chemokine, ligands for CCR4, were measured by ELISA in JRA synov ial fluid, JRA plasma, adult rheumatoid arthritis synovial fluid, and norma l plasma. IL-4 and IFN-gamma mRNA production was assessed in CD4(+)/CCR4(+) and CD4(+)/CCR4(-) cell subsets. We found accumulations of both CCR4(+) an d CCR5(+) T cells in JRA synovial fluids and a correlation for increased nu mbers of CCR4(+) T cells in samples collected early in the disease process. Thymus- and activation-regulated chemokine was detected in JRA synovial fl uid and plasma samples, but not in adult rheumatoid arthritis synovial flui d or control plasma. Macrophage-derived chemokine was present in all sample s. CD4(+)/CCR4(+) synovial lymphocytes produced more IL-4 and less IFN-gamm a than CD4(+)/CCR4(-) cells. These findings suggest that CCR4(+) T cells in the JRA joint may function early in disease in an anti-inflammatory capaci ty through the production of type 2 cytokines and may play a role in determ ining disease phenotype.