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The role of intraepithelial T cells in the pathogenesis of canine chronic enteropathies - A phenotypic characterization of intestinal intraepithelial lymphocytes of gastrointestinal healthy and chronic enteropathy dogs.
Phänotypische und funktionelle Charakterisierung intestinaler, intraepithelialer Lymphozyten von gesunden und chronischen Enterophathie-Hunden
Dissertation, Vet. Med. Univ. Wien, pp. 39.
Inflammatory bowel disease (IBD) of man and dog is an immunemediated disease of the gastrointestinal tract system. Although an increasing number of dogs suffer from IBD, little is known about the underlying multifactorial pathophysiology of this disease. In the healthy intestinal immune system intestinal intraepithelial lymphocytes (IEL) act as first line of defense against invading pathogens, but have also been identified as pro-inflammatory factors in human IBD and animal models. Alterations of IEL phenotypes in man and mouse affect disease onset and severity. This study was performed to get a better understanding in the canine IEL subsets by flow cytometry (FCM) and to elucidate their role in the pathogenesis of IBD. Furthermore, a more objective tool for the diagnostic work-up should be established. The study population consisted of 10 healthy and 10 IBD dogs of different breeds. Each animal was graded for clinical disease severity and all duodenal biopsy specimens were investigated histopathologically.
Isolated IEL from duodenal biopsies of both study groups were stained by three-colour FCM using anti-canine specific and anti-human cross-reactive antibodies against cell-surface markers to discriminate major lymphocyte subsets (CD3-12, TCR-ab, TCR-gd, CD4, CD8a and CD8b).
Initially, endoscopic biopsies were proven as suitable samples for FCM analyses. Clinical and pathohistologic indices of healthy dogs were significantly lower as compared to the IBD group. Healthy dogs had significantly lower numbers of TCR-gd+ T cells in comparison to the IBD dogs. Correlations, like in human medicine and animal models, between disease severity and IEL subsets could not be shown. Conclusively, FCM analyses of endoscopic biopsies are a suitable method for the canine IBD diagnostic work up. Our results showed differences in the IEL phenotypes between both study groups. For the first time FCM data, clinical and histopathologic scores of healthy and IBD dogs were collected and compared.