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[Anders Jahre Prize for young researchers 1994. Chronic intestinal inflammation studies with multi-colored
1Laboratorium for Immunhistokjemi og Immunpatologi (LIIPAT), Rikshospitalet, Oslo.
Abstract:
Multi-colour immunofluorescence can be a potent tool in investigating the cause of chronic inflammation of unknown etiology. The immune system uses two main mechanisms for target destruction; antibody-induced, complement-mediated or cell-mediated lysis. Immunohistochemical tracing of complement activation and immunoglobulin deposition in intestinal lesions from patients with ulcerative colitis and Crohn's disease show that ulcerative colitis may be an autoimmune disease characterized by an autoantibody of the IgG1 subclass to an apically located colonic autoantigen, which induce in situ complement activation and cellular lysis. The apical immune complex deposits co-localized with a previous identified putative autoantigen of 40kD, with peptide sequence homology with tropomyosin. Coeliac disease is a mucosal hypersensitivity to the wheat protein gluten. The intestinal lesion shows a peculiar disease specific increased percentage of T cell receptor (TCR)gamma/delta cells in the epithelium; differential use of CD45-isoforms and proliferative activation of intraepithelial T cells. T-helper(CD4) cells in the lamina propria show a non proliferative activation (CD25) which can be induced after gluten challenge in vitro. Immunomagnetic isolation of such in vitro activated T cells renders it possible to establish gluten reactive T cell clones that respond to gluten presented in the context of the disease associated human leucocyte antigen HLA-DQ2.