Based primarily on vitro studies, interleukin (IL)-2 has been considered a key growth and death factor for antigen-activated T lymphocytes. IL-2 is also essential to maintain self-tolerance, as IL-2- and IL-2 receptor-deficient mice exhibit lethal autoimmunity. The intrinsic death-sensitizing activity of IL-2 was thought to be a key mediator for apoptosis of peripheral autoreactive T cells. However, recent in vivo studies strongly favor a model whereby IL-2 controls autoimmunity through the production of CD4⁺CD25⁺ T regulatory (Treg) cells. In this setting, IL-2 is essential for expansion of Treg cells within the thymus and in peripheral neonatal-immune tissue. Thus, from being considered the primary growth factor for antigen-activated T lymphocytes, these new findings redefine the pivotal role for IL-2 as the major inducer for the developmental production of suppressive Treg cells.