Generalized Autoimmune Disease in interleukin-2-deficient Mice Is Triggered by an Uncontrolled Activation and Proliferation of CD4+ T Cells

Eur J Immunol. 1995 Nov;25(11):3053-9. doi: 10.1002/eji.1830251111.

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 auto-immune 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 (CD44high, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune / immunology
  • Anemia, Hemolytic, Autoimmune / mortality
  • Anemia, Hemolytic, Autoimmune / pathology
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / mortality
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Ligand
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interleukin-2 / deficiency*
  • Interleukin-2 / genetics
  • Ligands
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-2
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand