Induction and prevention of colonic inflammation in IL-2-deficient mice

J Immunol. 1997 Jan 15;158(2):566-73.


Gene-targeted mice deficient for IL-2 (IL-2 -/- mice) are free of apparent disease when maintained under germfree conditions but develop colitis and autoimmunity in a conventional environment. Here we show that colitis can be reproducibly induced in IL-2 -/- mice, but not in IL-2 +/+ mice, by i.p. immunization with Ag in CFA; thus enabling the systematic study of the immunopathogenesis of the colitis. We found that TNP-KLH or TNP-OVA had the most significant effect in inducing colitis, and while TNP-KLH immunization leads to the early appearance of activated T cells in the colons of both IL-2 -/- and IL-2 +/+ mice, only lamina propria cells of IL-2 -/- mice produced high amounts of INF-gamma. Moreover, both infiltrating colon CD4+ (69%) and CD8+ (6%) T cells secrete large amounts of IFN-gamma; however, only the depletion of CD4+ T cells leads to abrogation of the inflammation. In further analysis, we showed that the high IFN-gamma production is IL-12 driven, since colonic tissues of IL-2 -/- mice but not IL-2 +/+ mice show the presence of heterodimeric IL-12 and co-administration of anti-IL-12 with TNP-KLH completely prevented colitis and significantly reduced IFN-gamma production. Finally, we demonstrate that IL-2 -/- mice are deficient in their ability to induce Th2 responses after TNP-KLH challenge and that such immunization also leads to autoimmune-like phenomena in other organs of IL-2 -/- mice. These findings suggest that in the absence of IL-2 systemic administration of Ag induces primarily Th1 cells driven by overexpression of heterodimeric IL-12.

MeSH terms

  • Animals
  • Antigens, T-Independent / immunology
  • Colitis / chemically induced*
  • Colitis / immunology
  • Colitis / prevention & control*
  • Haptens / immunology
  • Hemocyanins / toxicity
  • Immunization
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / toxicity
  • Interleukin-12 / biosynthesis
  • Interleukin-2 / deficiency*
  • Interleukin-2 / genetics*
  • Interleukin-4 / biosynthesis
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutagenesis, Site-Directed / genetics
  • Ovalbumin / immunology
  • Ovalbumin / toxicity
  • T-Lymphocytes / metabolism
  • Trinitrobenzenes / immunology*
  • Trinitrobenzenes / toxicity*


  • Antigens, T-Independent
  • Haptens
  • Interleukin-2
  • Trinitrobenzenes
  • trinitrophenyl keyhole limpet hemocyanin
  • trinitrophenyl-ovalbumin
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin
  • Hemocyanins