Suppressor T cells - they're back and critical for regulation of autoimmunity!

Regulation of the immune response to self-antigens is a complex process tha t depends on maintaining self-tolerance while retaining the capacity to mou nt a robust immune response to foreign antigens. Autoreactive T cells speci fic for these autoantigens are present in most normal individuals but are k ept under control by multiple diverse peripheral tolerance mechanisms, in t he last few years, there has been a emergence of suppressor cells as among the most central of these regulatory mechanisms. These cells, which express CD4, CD25, and CD62L, develop in the thymus and survive in a CD28-dependen t manner in the periphery to maintain the homeostatic equilibrium of immuni ty and tolerance. In this review, we will summarize studies of these regula tory cells as they relate to autoimmune diseases and more specifically to t ype I diabetes and attempt to address some of the many outstanding question s. Finally, evidence is provided to support the ability of anti-CD3 mAbs to stimulate the regulatory T cells and reset the rheostat of immune toleranc e in an animal model of autoimmune diabetes, the NOD mouse.