Aberrant responsiveness to RANTES in synovial fluid T cells from patients with rheumatoid arthritis

• Published in: Journal of rheumatology Vol. 29; no. 6; pp. 1124 - 1134
• Main Authors: HISAKAWA, Naoko, TANAKA, Hirotoshi, HOSONO, Osamu, NISHIJIMA, Rikako, OHASHI, Yoshiyuki, SAITO, Seiji, NISHIYA, Koji, HASHIMOTO, Kozo, MORIMOTO, Chikao
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-06-2002; Journal of Rheumatology Publishing
• Subjects: Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; Biological and medical sciences; Case-Control Studies; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Chemokine CCL5 - pharmacology; Diseases of the osteoarticular system; Down-Regulation; Female; Flow Cytometry; Humans; Immunoblotting; Inflammatory joint diseases; Lymphocyte Activation - drug effects; Male; Medical sciences; Receptors, CCR5 - analysis; Receptors, CCR5 - drug effects; Reference Values; Sensitivity and Specificity; Synovial Fluid - cytology; Synovial Fluid - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Human; Immunopathology; Flow cytometry; Immune response; Pathogenesis; RANTES; Migration; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Cellular immunity; Chemotaxis; CCR5 chemokine receptor; Synovial fluid; Chronic; Immunoprecipitation reaction; Rheumatoid arthritis; T-Lymphocyte; Immunoblotting assay
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To study expression and function of the chemokine receptor CCR5 in synovial fluid (SF) T cells from patients with
rheumatoid arthritis (RA). METHODS: Expression of CCR5 was studied by flow cytometry and immunoblotting. The chemotactic response
of T cells to chemokines was studied in cell migration assay. Tyrosine phosphorylation of Crk-associated substrate lymphocyte-type
(CasL) was evaluated in immunoprecipitation and immunoblotting. RESULTS: SF T cells showed an increase in the population of
CCR5, CXCR4, and CD45RO positive cells and exhibited an increase in chemotactic activity, which was not augmented with RANTES
but stromal cell-derived factor-1alpha. Tyrosine phosphorylation per CasL molecule was markedly enhanced in SF T cells. In
H9 cells, tyrosine phosphorylation of not only focal adhesion kinase but also CasL was induced after treatment with RANTES.
Downmodulation of CCR5 by RANTES was decreased and recycling of CCR5 was accelerated in SF T cells when compared with peripheral
blood (PB) T cells. When CD45RO positive PB T cells were cultured with interleukin 2, blunted responsiveness to RANTES-induced
chemotaxis was reproduced as well as spontaneous chemotaxis, increased expression of CCR5, and aberrant receptor dynamics,
after RANTES stimulation as observed in SF T cells. CONCLUSION: Synovial fluid T cells highly positive for CCR5 show aberrant
characteristics; resistant to RANTES in terms of migration, but responsive in terms of dynamics of CCR5.