title: Aberrant responsiveness to RANTES in synovial fluid T cells from patients with rheumatoid arthritis.
abstract: 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.
authors.affiliation: Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hisakawa
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Hosono
authors.forename: Rikako
authors.initials: R
authors.lastname: Nishijima
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Saito
authors.forename: Koji
authors.initials: K
authors.lastname: Nishiya
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: 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
chemical_list: D018946:Chemokine CCL5; D019713:Receptors, CCR5