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    Faculty of Life Science, University of Manchester, Manchester

    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

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    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.

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    Description

    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
    Author(s) : Axel Roers, Lisa Siewe, Elke Strittmatter, Martina Deckert, Dirk Schlüter, Werner Stenzel, Achim D Gruber, Thomas Krieg, Klaus Rajewsky, Werner Müller
    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.
    Keywords : animals, gene silencing, gene silencing immunology, histological techniques, immunity, cellular, cellular immunology, innate, innate immunology, interleukin 10, interleukin 10 genetics, interleukin 10 metabolism, intestinal mucosa, intestinal mucosa patho

    Subject : unspecified
    Area : Other
    Language : English
    Year : 2004

    Affiliations Faculty of Life Science, University of Manchester, Manchester
    Journal : The Journal of Experimental Medicine
    Volume : 200
    Issue : 10
    Publisher : The Rockefeller University Press
    Pages : 1289-1297
    Url : http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2211912&tool=pmcentrez&rendertype=abstract
    Doi : 10.1084/jem.20041789

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