International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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ORAL PRESENTATION

TUESDAY 11 NOVEMBER
11:15 – 11:30 HRS

DYSREGULATION OF T CELL RESPONSES IN MICE WITH T CELL-SPECIFIC INACTIVATION OF THE IL-10 GENE

Mueller W
German Research Center for Biotechnology, Department of Experimental Dermatology

Co-Authors: 1) Roers A, 1) Siewe L,1) Strittmatter E, 2) Deckert M, 3) Schlüter D, 2) Stenzel W, 4) Gruber AD,1) Krieg T, 5) Rajewsky K
Institutions: 1) University of Cologne, Department of Dermatology, 2) University of Cologne, Department of Neuropathology, 3) University of Heidelberg, University Hospital Mannheim, 4) University of Hannover, School of Veterinary Medicine, Department of Pathology, 5) Harvard Medical School, Center for Blood Research

Interleukin-10 (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 using T cell-specific Cre/loxP-mediated targeting of the IL-10 gene. Splenocytes from mice with an inactivation of the IL-10 gene restricted to T cells secrete increased amounts of proinflammatory cytokines after activation in vitro compared to cells from control animals. The T cell-specific IL-10 mutants spontaneously develop chronic intestinal inflammation, 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, irritant responses of the skin are not enhanced in the T cell specific IL-10 mutant. We conclude that the regulation of T cell immunity is critically dependent on T cell-derived IL-10 while cutaneous innate inflammatory responses seem to be controlled by IL-10 from other cell types.