Normal Lymphoid Homeostasis and Lack of Lethal Autoimmunity in Mice Containing Mature T Cells with Severely Impaired IL-2 Receptors

Abstract

Abstract The importance of IL-2Rβ function for immune regulation is highlighted by the severe impairment in lymphoid cell function in IL-2Rβ-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 requirement for IL-2Rβ function in mature T lymphocytes. We show that transgenic thymic expression of the IL-2R β-chain in IL-2Rβ-deficient mice prevents lethal autoimmunity, restores normal production of B lymphocytes, and results in a peripheral T cell compartment that is responsive to triggering through the TCR, but not the IL-2R. The dysfunction of the IL-2R is illustrated 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-2Rα expression. These data indicate that lymphoid homeostasis is largely maintained despite a nonfunctional IL-2R in mature T lymphocytes and suggest that IL-2Rβ provides an essential signal during thymic development to regulate self-reactivity.