Open AccessSelective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis
Author(s) -
Wedderburn Lucy R.,
Robinson Nicola,
Patel Alka,
Varsani Hemlata,
Woo Patricia
Publication year - 2000
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200004)43:4<765::aid-anr7>3.0.co;2-b
Subject(s) - cxcr3 , synovial fluid , cytokine , immunology , arthritis , synovial membrane , juvenile rheumatoid arthritis , chemokine , immunophenotyping , cxcl10 , t cell , peripheral blood mononuclear cell , medicine , chemokine receptor , biology , pathology , inflammation , flow cytometry , in vitro , immune system , biochemistry , alternative medicine , osteoarthritis
Objective To study the expression of chemokine receptors CCR5 and CXCR3 and the Th1/Th2 cytokine balance in children with oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). Methods Using 3‐color immunofluorescence, we studied the expression of CCR5 and CXCR3 on, and T cell cytokine production by, paired samples of synovial fluid (SF) and peripheral blood (PB) T cells from 20 patients with oligoarticular‐ or polyarticular‐onset JIA. Chemokine and cytokine phenotypes were also compared within the CD45RO+,CD3+ subsets. CCR5 genotypes were confirmed by polymerase chain reaction typing and sequencing. Results In the majority of samples, the number of T cells that were CCR5+ and CXCR3+ was higher in SF than in PB, and this difference was significant. One child was homozygous for the null Δ32 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 CD45RO+ subset compared with PB CD45RO+ T cells. Conclusion The high expression of CCR5 and CXCR3 and high interferon‐γ: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 specific activation events have occurred in synovial T cells. We suggest that the highly activated, Th1‐type phenotype of T cells within the chronically inflamed joints of children with JIA may reflect specific recruitment events that contribute to the polarization of these cells.