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

• Published in: Cell Vol. 62; no. 3; pp. 457 - 467
• Main Authors: Tepper, Robert I., Levinson, Douglas A., Stanger, Ben Z., Campos-Torres, Juanita, Abbas, Abul K., Leder, Philip
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 10.08.1990; Cell Press
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Bone Marrow - pathology; DNA - genetics; DNA - isolation & purification; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Immunoglobulin; Humans; Hypersensitivity - genetics; Immunobiology; Immunoglobulin Heavy Chains - genetics; Immunoglobulins - analysis; Inflammation; Interleukin-4 - genetics; Lymphocyte Activation; Lymphokines, interleukins ( function, expression); Mice; Mice, Transgenic; Promoter Regions, Genetic; Regulatory factors and their cellular receptors; Spleen - immunology; T-Lymphocytes - immunology; Thymus Gland - immunology; Cell proliferation; Cell culture; Interleukin; Rodentia; Transgenic animal; Inflammation; Cell differentiation; Gene expression; Vertebrata; Mammalia; Mouse; Mechanism of action; Lymphocyte; ELISA assay; Histochemistry
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(90)90011-3

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 though 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.