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 from a breakdown of dominant tolerance mechanisms that normally control intestinal immunity. Although CD4+ T lymphocyte subpopulations and expression of MHC class II molecules have been shown to play a role in the pathogenesis of the disease, the nature of the responsible mechanisms remains unclear. In this paper we describe a novel mouse model for inflammatory bowel disease, 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 susceptibility of mice of the widely genetically manipulated C57BL/6 background), high reproducibility, and 100% penetrance, radiation-induced colitis will be a useful mouse model for colitis and a significant tool to study dominant immunological tolerance mechanisms. Moreover, our data imply that tolerization to enteric Ags requires MHC class II mediated presentation by APC of hemopoietic origin.
Marguerat
S
S
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
MacDonald
H R
HR
Kraehenbuhl
J P
JP
van Meerwijk
J P
JP
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D003092:Colitis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism* / Q000528:radiation effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000528:radiation effects; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma