Normal lymphoid homeostasis and lack of lethal autoimmunity in mice containing mature T cells with severely impaired IL-2 receptors

The importance of IL-2R beta function for immune regulation is highlighted by the severe impairment in lymphoid cell function in IL-2R beta-deficient mice. It has been speculated that failed IL-2/IL-2R signaling in peripheral T cells causes the associated autoimmunity, imbalanced peripheral lymphoid homeostasis, and defective T cell function. This study explored the requir ement for IL-2R beta function in mature T lymphocytes, We show that transge nic thymic expression of the IL-2R beta-chain in IL-2R beta-deficient mice prevents lethal autoimmunity, restores normal production of B lymphocytes, and results in a peripheral T cell compartment that is responsive to trigge ring through the TCR, but not the IL-2R. The dysfunction of the IL-2R is il lustrated by the near complete failure of mature T cells to proliferate to IL-2 in vitro and in vivo, to differentiate into CTL, and to up-regulate IL -2R alpha expression. These data indicate that lymphoid homeostasis is larg ely maintained despite a nonfunctional IL-2R in mature T lymphocytes and su ggest that IL-2R beta provides an essential signal during thymic developmen t to regulate self-reactivity.