CD4 Regulatory T Cells Prevent Lethal Autoimmunity in IL-2Rβ-Deficient Mice: Implications for the Nonredundant Function of IL-2

Abstract

Lethal autoimmunity associated with IL-2Rβ-deficient mice is prevented after thymic transgenic expression of wild-type IL-2Rβ in IL-2Rβ −/− mice (Tg −/− mice). Here, we show that CD4 +CD25 + regulatory T cells were not readily detected in IL-2Rβ −/− mice, but the production of functional CD4 +CD25 + T cells was reconstituted in Tg −/− mice. Adoptive transfer of normal CD4 +CD25 + T cells into neonatal IL-2Rβ-deficient mice prevented this lethal autoimmune syndrome. The CD4 +CD25 + T cells in disease-free adult IL-2Rβ-deficient recipient mice were present at a near normal frequency, were solely donor-derived, and depended on IL-2 for expansion. These observations indicate that the essential function of the IL-2/IL-2R system primarily lies at the level of the production of CD4 +CD25 + regulatory T cells.