CD25brightCD4⁺ regulatory T cells accumulate in inflamed joints of patients with chronic rheumatic disease

Background

CD25⁺CD4⁺ regulatory T cells participate in the regulation of immune responses. We recently demonstrated an enrichment of CD25brightCD4⁺ T cells with a capacity to control T cell proliferation in the joints of patients with rheumatoid arthritis (RA).

Objective

Here, we extend these studies to investigate a possible accumulation of regulatory T cells in the joints of other inflammatory diseases, and their potential to suppress cytokine production in patients with rheumatic diseases, including RA.

Methods

Synovial fluid and peripheral blood samples were obtained during relapse from 204 patients with spondyloarthropathies, juvenile chronic arthritis, and RA, and the frequency of CD25brightCD4⁺ T cells was determined. For functional studies, synovial cells from six patients were sorted by flow cytometry and the suppressive capacity of these CD25brightCD4⁺ T cells was determined in in vitro coculture.

Results

Of 204 patients, 198 patients exhibited a higher frequency of CD25brightCD4⁺ T cells in synovial fluid as compared with peripheral blood. Additionally, in comparison with healthy individuals, the patients had significantly fewer CD25brightCD4⁺ T cells in peripheral blood. Functionally, the CD25brightCD4⁺ T cells suppressed both type 1 and 2 cytokine production, and proliferation, independent of diagnosis.

Conclusion

Irrespective of diagnosis of the inflammatory joint disease, an accumulation of CD25brightCD4⁺ T cells in the joint and reduced numbers in peripheral blood suggest an active recruitment of regulatory T cells to the affected joint. Their capacity to suppress both proliferation and cytokine secretion might contribute to dampen the local inflammatory processes.