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mRNA Ratios1
William S. Rowe Division of Rheumatology, Children’s Hospital Medical Center, Cincinnati, OH 45229
To understand the mechanisms that promote recruitment and survival
of T cells within the pediatric inflamed joint, we have studied the
expression of CCR4 and CCR5 on synovial fluid T cells and matched
peripheral blood samples from juvenile rheumatoid arthritis (JRA)
patients using three-color flow cytometric analysis. Thymus- and
activation-regulated chemokine and macrophage-derived chemokine,
ligands for CCR4, were measured by ELISA in JRA synovial fluid, JRA
plasma, adult rheumatoid arthritis synovial fluid, and normal plasma.
IL-4 and IFN-
mRNA production was assessed in
CD4+/CCR4+ and
CD4+/CCR4- cell subsets. We found
accumulations of both CCR4+ and CCR5+ T cells
in JRA synovial fluids and a correlation for increased numbers of
CCR4+ T cells in samples collected early in the disease
process. Thymus- and activation-regulated chemokine was detected in JRA
synovial fluid and plasma samples, but not in adult rheumatoid
arthritis synovial fluid or control plasma. Macrophage-derived
chemokine was present in all samples.
CD4+/CCR4+ synovial lymphocytes produced more
IL-4 and less IFN- than CD4+/CCR4- cells.
These findings suggest that CCR4+ T cells in the JRA joint
may function early in disease in an anti-inflammatory capacity
through the production of type 2 cytokines and may play a role in
determining disease phenotype.
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