Regulatory T (T reg) cells found in the synovial fluid of inflamed joints can be identified by the coexpression of CD4, CD25, and CD27, according to Ruprecht and colleagues on page 1793.

CD4+ regulatory T cells in the synovial tissues of a juvenile arthritis patient coexpress CD25 (red) and CD27 (green).

Suppression of damaging T cell responses by CD4+ T reg cells is critical for the prevention of autoimmune disease. But studying these cells in the context of disease has been problematic, largely because CD4+ T reg cells and activated CD4+ T cells express many of the same surface molecules and are thus difficult to distinguish. Although coexpression of CD4 and the high affinity interleukin (IL)-2 receptor (CD25) identifies T reg cells in the circulation, CD25 cannot distinguish between T reg cells and local effector T cells, which up-regulate this molecule upon activation.

Ruprecht et al. now show that CD4+ CD25+ T reg cells found in the inflamed joints of children with autoimmune arthritis can be distinguished from their CD4+CD25+ effector T cell counterparts by the expression of the TNF receptor family member CD27—a molecule that is down-regulated on activated T cells. CD27 expression identified T reg cells in these patients, as the ability to suppress T cell proliferation in vitro resided solely in the CD4+CD25+CD27+ T cell subset.

But why does an autoimmune response develop in these patients despite an abundance of T reg cells at the site of disease? The authors suggest that the cytokines IL-7 and IL-15, which were detected in the patients' synovial fluid, might be to blame, as the combination of these cytokines reversed the in vitro ability of the T reg cells to inhibit T cell proliferation.