Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood

Objective. Our aim was to test the hypothesis that there is a deficit in the CD4(+)CD25(high) regulatory T-cell population in early rheumatoid arthritis (RA), either in size or functional activity. Methods. Peripheral blood mononuclear cells were examined from subjects with early active RA who had received no previous disease-modifying therapy (n=43), from individuals with self-limiting reactive arthritis (n=14), from subjects with stable, well-controlled RA (n=82) and from healthy controls (n=72). The frequencies of CD4(+)CD25(high) T-cells were quantified using flow cytometry, and function was assessed by the ability to suppress proliferation of CD4(+)CD25(-) T-cells. Paired blood and synovial fluid was analysed from a small number of RA and reactive arthritis patients. Results. There was a smaller proportion of CD4(+)CD25(high) T-cells in the peripheral blood of early active RA patients (mean 4.25%) than in patients with reactive arthritis or in controls (mean 5.90 and 5.30%, respectively, P= 0.001 in each case). Frequencies in stable, well-controlled RA (mean 4.63%) were not significantly different from early active RA or controls. There were no differences in suppressor function between groups. Higher frequencies of CD4(+)CD25(high) T-cells were found in synovial fluid than blood in both RA and reactive arthritis. Conclusions. These data demonstrate a smaller CD4(+)CD25(high) regulatory T-cell population in peripheral blood of individuals with early active RA prior to disease-modifying treatment. This may be a contributory factor in the susceptibility to RA and suggests novel approaches to therapy.