title: Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P- and E-selectin on T lymphocytes of patients with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To investigate P- and E-selectin ligand coexpression with chemokine receptors (CKRs) on T cells in the synovial fluid (SF) and blood of children with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Sixteen patients with polyarticular or persistent oligoarticular JIA (ages 5.3-15.1 years) were studied. SF and venous blood were collected, and immunostaining for the expression of CCR4, CCR5, CXCR3, and P- or E-selectin ligands was performed.
  
  
  RESULTS
  Compared to blood, SF was greatly enriched for CD4+ T cells bearing CCR5, CCR4, CXCR3, and both P- and E-selectin ligand. Twenty-five percent of the CD4+ T cells in SF expressed both CCR5 and CCR4, some also coexpressing CXCR3. Such cells were rare in blood. Half of the few CCR5+ T cells in blood coexpressed P- or E-selectin ligand, a phenotype that was enriched up to 50-fold in SF. A minority of CCR4+ and CXCR3+ cells in blood (∼25%) coexpressed selectin ligand; these were enriched 4-8-fold in SF. Most CCR4-expressing CD4+ T cells expressed both E-selectin ligand and cutaneous lymphocyte antigen.
  
  
  CONCLUSIONS
  CCR4-, CCR5-, CXCR3-, and selectin ligand-expressing CD4+ T cells preferentially accumulate in the joints of children with JIA. The marked enrichment of CCR5+ T cells coexpressing P-selectin and/or E-selectin ligand in CD4+ SF T cells suggests that the few such cells in blood selectively migrate to inflamed joints via endothelial P- and E-selectin- and CCR5-activating chemokines. The predominance of CCR4-expressing CD4+ T cells coexpressing E-selectin ligand suggests that such cells migrate not only to areas of cutaneous inflammation, as previously reported, but also to the joints in JIA. Combined targeting of CCR5- and E-selectin-dependent mechanisms may be a relevant treatment strategy.
authors: Dalhousie University, Halifax, Nova Scotia, Canada. andrew.issekutz@iwk.nshealth.ca
authors: Andrew C
authors: AC
authors: Issekutz
authors: Patrick J
authors: PJ
authors: Quinn
authors: Bianca
authors: B
authors: Lang
authors: Suzanne
authors: S
authors: Ramsey
authors: Adam M
authors: AM
authors: Huber
authors: Derek
authors: D
authors: Rowter
authors: Mohan
authors: M
authors: Karkada
authors: Thomas B
authors: TB
authors: Issekutz
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3