Background
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Despite the accumulation of evidence that CD4^+^CD25^high^regulatory T cells play an important role in the prevention of autoimmune disease, little is known about how they are regulated *in vivo*.  There are thought to be at least two mechanisms for the generation of regulatory T cells: naturally occurring CD4^+^CD25^high^regulatory T cells derive from the thymus, and peripherally-induced regulatory cells arise under tolerogenic conditions.  Recently, cytokine activation requirements for CD4^+^CD25^high^regulatory T-cell function were associated with IL-7, as well as IL-2 and IL-4.  We examined a cohort of patients with rheumatoid arthritis whose disease was well controlled, and where we had previously shown that heterogeneous circulating levels of IL-7 positively correlated with thymic activity, to investigate the role of IL-7 on the function of CD4^+^CD25^high^T cells. 

Methods
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Peripheral blood samples were taken from patients with rheumatoid arthritis whose disease was well controlled.  Serum IL-7 levels were measured by ELISA.  Quantification of the CD4^+^CD25^high^T-cell subset was performed using flow cytometry.  Thymic activity was evaluated by real-time PCR quantification of T-cell receptor excision circles in CD4^+^T cells.  Thymidine incorporation assays were used to assess the response of CD4^+^CD25^high^T cells to IL-7 stimulation, and also their ability to suppress the proliferation of CD4^+^CD25^-^T cells in response to phytohaemagglutinin in co-culture. 

Results
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Circulating levels of IL-7 positively correlated with the frequency of circulating CD4^+^CD25^high^T cells (*n*= 47, *R*= 0.647, *P*\< 0.0001).  This appeared to result from an increased production of these cells by the thymus.  High levels of circulating IL-7 *in vivo*were associated with increased suppressor functions of CD4^+^CD25^high^T cells *in vitro*(*n*= 5, mean 79% suppression by cells from patients with high IL-7 levels, and 39% suppression by cells from patients with low IL-7 levels).  In patients with low circulating IL-7 levels, adding exogenous IL-7 to co-cultures appeared to increase suppression. 

Conclusions
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Our data suggest that IL-7 has a role in regulating CD4^+^CD25^high^T-cell number and function.  Circulating IL-7 levels are low in active rheumatoid arthritis, and this may be a contributory factor to the reduced size and suppressor function of the CD4^+^CD25^high^regulatory T-cell population in this disease.