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


CONCLUSIONS
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.
Hisakawa
Naoko
N
Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
Tanaka
Hirotoshi
H
Hosono
Osamu
O
Nishijima
Rikako
R
Ohashi
Yoshiyuki
Y
Saito
Seiji
S
Nishiya
Koji
K
Hashimoto
Kozo
K
Morimoto
Chikao
C
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D019713:Receptors, CCR5 / Q000032:analysis* / Q000187:drug effects*; D012016:Reference Values; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018946:Chemokine CCL5; D019713:Receptors, CCR5