IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice

Cell. 1990 Aug 10;62(3):457-67. doi: 10.1016/0092-8674(90)90011-3.

Abstract

We have assessed the biologic role of IL-4 by fusing its gene to an immunoglobulin promoter/enhancer and introducing it into transgenic mice. By attenuating the transgene promoter through the insertion of E. coli lac operator sequences, we have created a series of animals that constitutively express varying amounts of IL-4. Overexpression of IL-4 results in a marked increase in serum IgE levels and the appearance of an inflammatory ocular lesion (blepharitis) with characteristic histopathologic features seen in allergic reactions. In addition, expression of the IL-4 transgene in the thymus perturbs T cell maturation, reducing the population of immature CD4+CD8+ thymocytes and peripheral T cells while increasing the population of mature CD8+ thymocytes. These results demonstrate that deregulation of a single cytokine gene in vivo can induce a complex inflammatory reaction resembling that observed in human allergic disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / pathology
  • DNA / genetics
  • DNA / isolation & purification
  • Enhancer Elements, Genetic
  • Genes, Immunoglobulin
  • Humans
  • Hypersensitivity / genetics*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulins / analysis
  • Inflammation
  • Interleukin-4 / genetics*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulins
  • Interleukin-4
  • DNA