Helicobacter hepaticus infection triggers inflammatory bowel disease in T cell receptor alphabeta mutant mice

Abstract

The T cell receptor alpha chain-deficient (TCR alpha-/-) and TCR beta chain-deficient (TCR beta-/-) mice develop chronic intestinal inflammation that resembles inflammatory bowel disease by 3 to 4 months of age. The objective of the study reported here was to determine the role of infection with the bacterial pathogen Helicobacter hepaticus in the pathogenesis of disease in TCR alphabeta mutant mice. The H. hepaticus-infected TCR alphabeta mutant mice were rederived by use of embryo transfer to produce Helicobacter-free animals. Helicobacter-free TCR alpha-/-, TCR beta-/-, and TCR alpha-/- beta-/- mice were inoculated with H. hepaticus. Experimentally infected mice and uninfected control mice were examined for intestinal lesions at 3, 6, and 9 months after inoculation. The TCR alphabeta mutant mice inoculated with H. hepaticus developed intestinal epithelial cell hyperplasia and mucosal inflammation. By 6 months after inoculation, infected animals had moderate cecal and colonic lesions. Helicobacter-free TCR alpha-/- mice, but not TCR beta-/- or TCR alpha-/- x beta-/- mice, also developed H. hepaticus-independent colitis by 9 months after inoculation. Infection with H. hepaticus is sufficient to cause chronic proliferative intestinal inflammation in TCR alphabeta mutant mice. However, H. hepaticus infection is not necessary for intestinal disease in TCR alpha-/- mice.