Comment

The role of antigen specific T lymphocytes in mediating food sensitive enteropathies such as coeliac disease has been suggested for many years,1 but the link between specific T cell activation and intestinal pathology has been difficult to prove directly. This partly reflects the absence of suitable animal models in which mucosal T cells can be activated by dietary antigens, owing to the fact that immunological tolerance is the usual result of feeding dietary protein antigens to animals.2 3 Therefore the recent paper by Newberry et al describing the induction of small bowel enteropathy in mice fed hen egg lysozyme (HEL) as a representative dietary protein, is a welcome and interesting addition to the field.

Activation of mucosal CD4+ T cells by alloantigens during a graft-versus-host reaction (GvHR) in experimental mice,4 5 or by mitogens in explants of human fetal intestine in vitro6 7 can produce a pattern of small bowel pathology similar to that in coeliac disease, with crypt hypertrophy, epithelial cell hyperplasia and villus atrophy. However, these models clearly cannot reproduce local T cell responses to food proteins and, in both cases, the pathology often progresses to complete mucosal destruction, a feature not usually associated with coeliac disease. Similarly, although it is possible to induce crypt hyperplasia in the jejunum by oral challenge with ovalbumin (OVA) in mice in whom oral tolerance has been abrogated experimentally,3 8 the resulting intestinal pathology is mild, with the hallmark feature of coeliac disease, villus atrophy, not being found. This may reflect the low proportion of food antigen specific T cells in normal animals.

In their paper, Newberry et al make use of T cell receptor (TcR) transgenic mice backcrossed on to a TcRα KO background. As this ensures that there are no T cells expressing endogenously rearranged …