The Immune System and Mucosal Transformation – Historical Perspective

Abstract

An intimate association between columnar epithelial cells and lymphocytes within the epithelial layer of the gut and other organs has been recognised for more than a century. Various roles have been postulated for intraepithelial lymphocytes (IEL), nutritive as well as immunopathological. Recently, the relevance of activation of mucosal lymphocytes to some of the developmental changes in the gut at weaning have been hypothesised, and the relevance of the IEL to the induction of specialised epithelium overlying Peyer’s patches remains to be established.Interactions between lymphocytes and the structure of the gut mucosa can readily be studied by using defined animal models in which the state of development of the gut, luminal antigens and bulking agents, host factors such as nutritional status can be defined, and against such background various forms of immune-mediated intestinal injury can be created. The earliest work along these lines was purely descriptive, particularly of the weaning changes, and also concerned the lymphocyte mediated gut damage of allograft rejection and later other models of T cell injury. These experiments clearly showed stimulation of crypt mitosis in immune mediated enteropathy, with crypt hyperplasia, which could not be explained by a feedback stimulation from damaged villi or villus enterocytes. Further work is now showing that mediators released by lamina propria activated T cells influence mitotic activity and differentiation of crypt enterocytes, as well as modifying the rate and patterns of expression of brush border enzymes and expression of cell surface class II HLA antigens. New approaches to the investigation of interactions between T cells and the epithelium of the gut include the use of organ culture of mucosal biopsies, studies of antigen specific reactions, particularly in coeliac disease, by in vivo challenge as well as in vitro, and the use of intestinal epithelially derived cell lines. The responses of the colonic and small bowel mucosae are not entirely analogous, and only limited studies have so far investigated the immunological stimuli for colonic cell proliferation and malignant transformation.