title: T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation.
abstract: Interleukin (IL)-10 is a regulator of inflammatory responses and is secreted by a variety of different cell types including T cells. T regulatory cells have been shown to suppress immune responses by IL-10-dependent, but also IL-10-independent, mechanisms. Herein, we address the role of T cell-derived IL-10 in mice with an inactivation of the IL-10 gene restricted to T cells generated by Cre/loxP-mediated targeting of the IL-10 gene. Splenocytes from this T cell-specific mutant secrete increased amounts of proinflammatory cytokines after activation in vitro compared with show enhanced contact hypersensitivity reactions, and succumb to severe immunopathology upon infection with Toxoplasma gondii. Despite intact IL-10 genes in other cell types, the dysregulation of T cell responses observed in the T cell-specific IL-10 mutant closely resembles the phenotype in complete IL-10 deficiency. However, in contrast to complete IL-10 deficiency, sensitivity to endotoxic shock and irritant responses of the skin are not enhanced in the T cell-specific IL-10 mutant. Our data highlight the importance of T cell-derived IL-10 in the regulation of T cell responses and demonstrate that endotoxic shock and the irritant response of the skin are controlled by IL-10 from other cell types.
authors.affiliation: Dept. of Dermatology, University of Cologne, Josef Stelzmann Str. 9, 50931 Cologne, Germany. axel.roers@uni-koeln.de
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Lisa
authors.initials: L
authors.lastname: Siewe
authors.forename: Elke
authors.initials: E
authors.lastname: Strittmatter
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.forename: Dirk
authors.initials: D
authors.lastname: Schlüter
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
mesh_terms: D000818:Animals; D020868:Gene Silencing / Q000276:immunology*; D006652:Histological Techniques; D007111:Immunity, Cellular / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D023422:Skin Irritancy Tests; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10