Protection from radiation-induced colitis requires MHC class II antigen expression by cells of hemopoietic origin

Ulcerative colitis, an inflammatory bowel disease, is believed to result fr om a breakdown of dominant tolerance mechanisms that normally control intes tinal immunity, Although CD4(+) T lymphocyte subpopulations and expression of MHC class II molecules have been shown to play a role in the pathogenesi s of the disease, the nature of the responsible mechanisms remains unclear. In this paper we describe a novel mouse model for inflammatory bowel disea se, radiation-induced colitis, that occurs with complete penetrance 6-8 wk postinduction. A combination of high dose gamma-irradiation and lack of MHC class II expression on cells of hemopoietic origin results in development of colitis in C57BL/6 mice. Because of its versatility (due to susceptibili ty of mice of the widely genetically manipulated C57BL/6 background), high reproducibility, and 100% penetrance, radiation-induced colitis will be a u seful mouse model for colitis and a significant tool to study dominant immu nological tolerance mechanisms, Moreover, our data imply that tolerization to enteric Ags requires MHC class II mediated presentation by APC of hemopo ietic origin.