Chemokine receptor CCR4 on CD4+ T cells in juvenile rheumatoid arthritis synovial 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 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-gamma 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-gamma 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.
Thompson
S D
SD
William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. thoms0@chmcc.org
Luyrink
L K
LK
Graham
T B
TB
Tsoras
M
M
Ryan
M
M
Passo
M H
MH
Glass
D N
DN
D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D016207:Cytokines; D008024:Ligands; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma