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 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 A32 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.


CONCLUSIONS
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 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.
Wedderburn
L R
LR
Department of Molecular Pathology, University College, London, UK.
Robinson
N
N
Patel
A
A
Varsani
H
H
Woo
P
P
D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000097:blood* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D010641:Phenotype; D019713:Receptors, CCR5 / Q000235:genetics*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
C515187:CXCR3 protein, human; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma