Synovial and Peripheral Blood CD4+FoxP3+ T Cells in Spondyloarthritis

Objective. Regulatory T cells are characterized by expression of the transcription factor FoxP3 and are thought to be involved in the pathogenesis of autoimmune diseases. We determined the frequency and phenotypic characteristics of CD4+FoxP3+ T cells in the blood and synovial fluid (SF) of patients with inflammatory joint diseases. Methods. SF from 10 patients with ankylosing spondylitis (AS), 20 patients with other spondyloarthritides or with peripheral arthritis (pSpA), and 12 patients with rheumatoid arthritis (RA), and peripheral blood (PB) from 22 patients with AS, 19 with pSpA, 15 with RA, and 12 healthy controls were stained for CD4, FoxP3, CD25, and CD 127 and different effector cytokines and then analyzed by flow cytometry. Methylation pattern of the Treg-specific demethylated region (TSDR) was determined after bisulfite treatment by quantitative polymerase chain reaction. Results. In all groups of patients we observed higher frequencies of Foxp3+ cells/CD4+ T cells within SF compared to PB. The frequency of synovial Foxp3+ cells/CD4+ T cells was significantly higher in patients with pSpA (18.79% +/- 6.41%) compared to patients with AS (9.69% +/- 4.11%) and patients with RA (5.95% +/- 2.21%). CD4+FoxP3+ T cells were CD25+ and CDI27- and lacked effector cytokine production in any of the different patient groups. The majority of the CD4+CD25+CDI27- T cells showed demethylation of the TSDR within the Foxp3 locus, confirming its regulatory phenotype. Conclusion. Our data show accumulation of Foxp3+ T cells within inflamed joints. These Foxp3+ T cells are mainly of stable T regulatory phenotype. The high frequency of Foxp3+ T cells in pSpA might contribute to the spontaneous resolution and remitting course of arthritis in pSpA as compared to the more persistent joint inflammation in RA. (First Release Sept 15 2011; J Rheumatol 2011;38:2445-51; doi:10.3899/jrheum.110377)