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

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Abstract
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.

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