Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody

Abstract

The isolation of gliadin specific HLA-DQ2 restricted T lymphocyte clones from the intestinal mucosa of patients with coeliac disease supports a role for cell mediated immunity in the pathogenesis of this condition. Whether supernatants from immune activated T cell clones could produce histological damage to duodenal mucosa in vitro was studied. Biopsy specimens were obtained from 18 patients without coeliac disease or any other demonstrable abnormality. The tissue was maintained in organ culture for 24 hours with organ culture medium alone, with supernatant from gliadin sensitive T cell clones that had (B) or had not (A) been stimulated with gluten, and compared with the effects caused by the addition of interferon gamma to the organ culture medium. Both the (B) supernatants (1:100) and interferon gamma (100 IU/ml) produced a significant reduction in the enterocyte height (21:5 (3.4) microns and 21.0 (3.2) microns respectively, each p < 0.001) compared with specimens grown in organ culture medium alone (27.3 (2.8) microns). The toxic effects of (B) supernatants could be blocked by pre-incubating them with anti-interferon gamma antibody. These findings support the role of gliadin sensitive T lymphocytes in the immune pathogenesis of coeliac disease and their secretion of interferon gamma may cause the damage to enterocytes observed in this condition.