International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 126 - CD4+ T CELL MEDIATED CHRONIC INTESTINAL DISEASE: IMMUNE REGULATION VERSUS INFLAMMATION

Westendorf AM
German Research Centre for Biotechnology, Braunschweig, Germany

Co-Authors: Geffers R, Templin M, Buer J, Bruder D.
Institutions: German Research Centre for Biotechnology, Braunschweig, Germany

Several studies have suggested that chronic inflammatory bowel disease might be a consequence of antigen specific recognition of appropriate T cells which expand and induce immunopathology. To analyze the immunological and molecular mechanisms of antigen specific CD4+ T cell response in chronic mucosal inflammation a transgenic mouse expressing hemagglutinin (HA) in enterocytes of the intestinal epithelium was generated. Concomitant expression of HA and a MHC class II-restricted T cell receptor specific for HA resulted in an autoimmune mediated chronic inflammation accompanied by activation of peripheral HA specific lymphocytes and lymphocytic infiltration in the Lamina propria and intestinal epithelium. The mild form of mucosal inflammation suggested the induction of peripheral tolerance mechanisms. To study these mechanisms in more detail, extensive immunological characterization of self reactive LPL and IEL isolated from the inflamed intestine was performed by cellular assays and global gene expression profiling. Enterocyte specific LPL and IEL show a reduced reactivity to their corresponding antigen and secrete lower amounts of inflammatory cytokines in vitro. Moreover, mucosal inflammation was accompanied by brought changes in the gene expression pattern of LPL and IEL. Profiling revealed differential expression of proinflammatory genes, as well as a remarkable set of genes discussed in the context of immune regulation.

Together, our model will permit us to carefully dissect the mechanisms by which enterocytes specific LPL and IEL regulate the priming and/or effector function underlying chronic intestinal inflammation.


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