Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P‐ and E‐selectin on T lymphocytes of patients with juvenile idiopathic arthritis

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.

Conclusion

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.