PT  - JOURNAL ARTICLE
AU  - Naoko Hisakawa
AU  - Hirotoshi Tanaka
AU  - Osamu Hosono
AU  - Rikako Nishijima
AU  - Yoshiyuki Ohashi
AU  - Seiji Saito
AU  - Koji Nishiya
AU  - Kozo Hashimoto
AU  - Chikao Morimoto
TI  - Aberrant responsiveness to RANTES in synovial fluid T cells from patients with rheumatoid arthritis.
DP  - 2002 Jun 01
TA  - The Journal of Rheumatology
PG  - 1124--1134
VI  - 29
IP  - 6
4099  - http://www.jrheum.org/content/29/6/1124.short
4100  - http://www.jrheum.org/content/29/6/1124.full
SO  - J Rheumatol2002 Jun 01; 29
AB  - 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.