Studies of intestinal lymphoid tissue. XI--The immunopathology of cell-mediated reactions in gluten sensitivity and other enteropathies.

Computerised image-analysis was used to quantitate small intestinal mucosae from celiac sprue and dermatitis herpetiformis patients, Gambian children with tropical-sprue-like malabsorption, first-degree celiac sprue relatives, and treated celiac sprue patients during challenge with a peptic-tryptic digest of gluten. A wide range of mucosal appearances was observed. Typically, 'flat' lesions (Type 2) revealed a reduced number of epithelial lymphocytes that were large and mitotically active. At the other extreme, mucosal architecture was relatively well preserved (Type 1) but surface epithelium contained an expanded population of small, non-mitotic lymphocytes, with or without crypt hyperplasia. Similar changes were observed in one-third of celiac relatives and following small dose gluten challenge. Larger dose challenges revealed a transition from Type 1 to Type 2 lesions over a 5-day period. Studies in a few patients over 2-4 years showed a similar type of progression. A major feature of this sequence was early appearance of crypt hypertrophy while villi persisted, indicating a role for factors other than increased loss of enterocytes from surface epithelium. These changes parallel the T lymphocyte-mediated events in graft-versus-host reactions in animals. It is thus concluded that the spectrum of immunopathologic changes observed in gluten sensitivity is fundamentally a cell-mediated effect, the degree of change being controlled by host genetic factors. In becoming flat, it appears obligatory for the mucosa to evolve through the earlier Type 1 lesion in which crypt hypertrophy is a prominent response.