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.

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.

FigureCD4^+^ regulatory T cells in the synovial tissues of a juvenile arthritis patient coexpress CD25 (red) and CD27 (green).

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.

[^1]: <hvanepps@rockefeller.edu>
