IMMUNOLOGICAL BASIS FOR CELIAC-DISEASE, INFLAMMATORY BOWEL-DISEASE, AND TYPE B CHRONIC GASTRITIS

Celiac disease is an interesting model for immunopathology operating in the gastrointestinal mucosa. An early event is stimulation of the secretory immune system but this does not explain the flat lesion. Local and systemic overproduction of IgG antibodies to gluten apparently leads to subepithelial complement activation, which may cause epithelial damage and compensatory crypt hyperplasia. However, proliferation of crypt cells may be induced chiefly by cytokines released from activated T lymphocytes and perhaps macrophages. Presentation of gluten peptides to T cells is probably in some way related to the genetic susceptibility to celiac disease, which has been mapped to an HLA-DQ alpha/beta heterodimer; but some additional factor must be involved, perhaps a virus infection. The striking accumulation of T cells in the epithelium early in disease activation is intriguing, particularly the high and fairly specific fraction bearing the gamma/delta T-cell receptor. Nevertheless, these intraepithelial lymphocytes do not seem to cause villous atrophy because the T-cell receptor gamma/delta-+ cells are increased also in treated patients who show normal villi. The role of the T-cell receptor gamma/delta-+ subset, as well as that of the dominating T-cell receptor alpha/beta-+ intraepithelial lymphocytes, therefore remains unknown. Activation of mucosal T cells and macrophages is also a prominent feature of inflammatory bowel disease but virtually nothing is known about the initiating event(s). There is a dramatic local overproduction of IgG1 in the established lesion, the IgG1 subclass being favored in ulcerative colitis, apparently on a genetic basis. The local IgG1 response in ulcerative colitis seems to reflect an autoimmune reaction against the colonic surface epithelium, which by complement activation may cause ulceration and persistent inflammation. Much interest is currently focused on Helicobacter pylori as a causative factor in type B chronic gastritis, but it remains to be shown whether this bacterium explains the local activation of the T-cell system and mucosal overproduction of IgG seen also in this disorder.