Transgenic mouse model of intestine-specific mucosal injury and repair.

Abstract

Most studies of injury and repair to mucosal tissue have used nonspecific mediators to induce injury. Damage to the mucosal epithelium resulting from chemical or radiation treatment associated with cancer therapy may fall into this category of injury. When such treatments are applied, it is generally not possible to predict or control the extent of possible injury. This fact makes analysis of inductive and reparative processes difficult. In addition, the role of the immune system in the etiology and subsequent healing of mucosal tissue following cancer therapy with or without bone marrow transplantation remains unclear. To study tissue- and antigen-specific immune damage of intestinal mucosal tissue, we generated transgenic mice that express a nominal antigen exclusively in intestinal epithelial cells. The transfer of antigen-specific CD8 T cells with concomitant virus infection resulted in the destruction of intestinal epithelial cells and disease. The destructive phase in some cases was followed by complete recovery and tolerance induction. This model will provide a system that can be regulated for analysis of the mediators of mucosa-specific tissue damage and repair.