Role of regulatory T cells in experimental arthritis and implications for clinical use

In recent years the T-regulatory (CD4+CD25+ Treg) storm has remodelled the immunology landscape. Since the original reports of a suppressive activity of CD4+CD25+ Treg, in the mid-1980s, an exponential number of papers have appeared in the literature. The employment of CD4+CD25+ Treg for therapeutic purposes is now one of the 'holy grails' in immunology and much effort is focused on the exploitation of this therapeutic avenue. In the last issue of Arthritis Research & Therapy, Frey and colleagues [1] provide an additional piece to the CD4+CD25+ Treg jigsaw. In most autoimmune diseases (in humans or in animal models) Treg have been identified [2,3]. In all tested models these cells were capable of preventing or partly inhibiting the induction of an autoimmune response. The absence of Treg, either due to a Foxp3 genetic defect such as that in patients with IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) [4] or scurfy mice [5] or by means of depletion with anti-CD25 monoclonal antibodies in animal models, favours the initiation of a variety of autoimmune diseases [3]. Conversely, the adoptive transfer of CD4+CD25+ T cells prevents the induction of autoimmune responses [3]. The important role of CD4+CD25+ Treg during the induction phase of autoimmunity has also been previously confirmed in collagen-induced arthritis [6], one of the most widely used RA animal models [7].Frey and colleagues [1] show that CD4+CD25+ Treg also have a fundamental role in the experimental antigen-induced arthritis. However, not all RA animal models seem to respond to CD4+CD25+ Treg manipulation as described in proteoglycan-induced arthritis [8]. On this backdrop the paper by Frey and colleagues represents only a minor blink of an eye in the vast Treg literature, but Frey and colleagues introduce a provocative 'spin' to their results as they question the potential of the 'therapeutic' role of Treg on established autoimmune diseases. In this model, adoptive transf