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

Axel Roers, Lisa Siewe, Elke Strittmatter, Martina Deckert, Dirk Schlüter, Werner Stenzel, Achim D. Gruber, Thomas Krieg, Klaus Rajewsky, Werner Müller

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)1289-1297
    Number of pages8
    JournalJournal of Experimental Medicine
    Volume200
    Issue number10
    DOIs
    Publication statusPublished - 15 Nov 2004

    Keywords

    • Allergic contact dermatitis
    • Cytokines
    • Gene targeting
    • Inflammation
    • Inflammatory bowel disease

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