Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis

Objective. To study the expression of chemokine receptors CCR5 and CXCR3 an d the Th1/Th2 cytokine balance in children with oligoarticular or polyartic ular juvenile idiopathic arthritis (JIA). Methods. Using 3-color immunofluorescence, we studied the expression of CCR 5 and CXCR3 on, and T cell cytokine production by, paired samples of synovi al fluid (SF) and peripheral blood (PB) T cells from 20 patients with oligo articular- or polyarticular-onset JIA, Chemokine and cytokine phenotypes we re also compared within the CD45RO+,CD3+ subsets. CCR5 genotypes were confi rmed by polymerase chain reaction typing and sequencing. Results. In the majority of samples, the number of T cells that were CCR5and CXCR3+ was higher in SF than in PB, and this difference was significant . One child was homozygous for the null Delta 32 CCR5 allele; 4 others had lower expression of CXCR3 in SF than in blood, All samples showed strongly Th1-type cytokine production by synovial T cells compared with that by PB T cells. Both features were also markedly polarized within the synovial CD45 RO+ subset compared with PB CD45RO+ T cells. Conclusion. The high expression of CCR5 and CXCR3 and high interferon-gamma :interleukin-4 ratios suggest a type 1 phenotype of SF T cells in JIA. The difference between CD45RO+ T cells from SF and from PB suggests that specif ic activation events have occurred in synovial T cells. We suggest that the highly activated, Th1-type phenotype of T cells within the chronically inf lamed joints of children with JIA may reflect specific recruitment events t hat contribute to the polarization of these cells.