IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice.
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.
Tepper
R I
RI
Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Levinson
D A
DA
Stanger
B Z
BZ
Campos-Torres
J
J
Abbas
A K
AK
Leder
P
P
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007136:Immunoglobulins / Q000032:analysis; D007249:Inflammation; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D015847:Interleukin-4; D004247:DNA