CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2.

Lethal autoimmunity associated with IL-2Rbeta-deficient mice is prevented after thymic transgenic expression of wild-type IL-2Rbeta in IL-2Rbeta(-/-) mice (Tg -/- mice). Here, we show that CD4(+)CD25(+) regulatory T cells were not readily detected in IL-2Rbeta(-/-) 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-2Rbeta-deficient mice prevented this lethal autoimmune syndrome. The CD4(+)CD25(+) T cells in disease-free adult IL-2Rbeta-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.