CD4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas

The immune system requires a homeostatic equilibrium between the mechanisms that assure self-tolerance, those that control the capacity to mount life-long immunity to pathogenic microbes, and those that attenuate effector mechanisms from inducing immune pathology [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance . Cell 2008, 133 (5):775–87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4 + CD25 + regulatory T cells . Trends Immunol 2004, 25 :374–80]. In the past decade, an overwhelming body of literature showed that CD4 + Foxp3 + regulatory T (Treg) cells are a dominant mechanism regulating the decision fate of these different immunological outcomes. Indeed, CD4 + Foxp3 + Treg cells develop largely in the thymus but can be induced in the periphery throughout the course of immune responses [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance . Cell 2008, 133 (5):775–87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4 + CD25 + regulatory T cells . Trends Immunol 2004, 25 :374–80]. Treg cells have emerged as a central control point in the regulation of autoimmune responses. Despite progress made in various in vitro and in vivo models, much uncertainty exists over their mechanism of action in vivo . Here, we summarize research characterizing the functional dynamics of CD4 + Foxp3 + Treg cells in the control of autoimmunity in rodents and humans.