Generalized autoimmune disease in interleukin‐2‐deficient mice is triggered by an uncontrolled activation and proliferation of CD4⁺ T cells

TLDR

IL‑2‑deficient BALB/c mice develop a lymphoproliferative syndrome with severe hemolytic anemia and die within five weeks, accompanied by autoantibodies and organ inflammation indicative of a generalized autoimmune disease. Early after birth, IL‑2‑deficient mice show increased lymphocyte proliferation and polyclonal activation, and treatment with anti‑gp39 (CD40L) antibody blocks disease, demonstrating that activated CD4⁺ T cells are the initial immune alteration and that IL‑2 is essential for maintaining self‑tolerance.

Abstract

Abstract Interleukin‐2‐deficient mice (IL‐2 −/− ) crossed to a BALB/c genetic background develop a lymphoproliferative syndrome with severe hemolytic anemia and die within 5 weeks of age. The presence of autoantibodies of various specificities and inflammatory lesions in several organs are indicative of a generalized autoimmune disease. No alterations of the immune system were observed in 6‐day‐old animals, but 10‐day‐old mice already showed an increased proliferation and polyclonal activation of lymphocytes. The treatment of IL‐2 −/− mice with anti‐gp39(CD40L) antibody prevented the disease and indicated that the appearance of activated CD4 + T cells (CD44 high , CD69 + ) represents the first alteration of the immune system in IL‐2 −/− mice. Collectively, our results suggest that an essential role of IL‐2 in vivo , which is not compensated by other cytokines, is the maintenance of self tolerance.