Role of regulatory T-cells in autoimmunity

There has been considerable historical interest in the concept of a specialist T-cell subset which suppresses over-zealous or inappropriate T-cell responses. However, it was not until the discovery that CD4⁺CD25⁺ T-cells had suppressive capabilities both in vitro and in vivo that this concept regained credibility and developed into one of the most active research areas in immunology today. The notion that in healthy individuals there is a subset of T_reg-cells (regulatory T-cells) involved in ‘policing’ the immune system has led to the intensive exploration of the role of this subset in disease resulting in a number of studies concluding that a quantitative or qualitative decline in T_reg-cells is an important part of the breakdown in self-tolerance leading to the development of autoimmune diseases. Although T_reg-cells have subsequently been widely postulated to represent a potential immunotherapy option for patients with autoimmune disease, several studies of autoimmune disorders have demonstrated high numbers of T_reg-cells in inflamed tissue. The present review highlights the need to consider a range of other factors which may be impairing T_reg-cell function when considering the mechanisms involved in the breakdown of self-tolerance rather than focussing on intrinsic T_reg-cell factors.