Abstract
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.
MeSH terms
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Animals
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / radiation effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / radiation effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / radiation effects
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Colitis / genetics*
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Colitis / immunology*
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Colitis / pathology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / radiation effects
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Hematopoietic Stem Cells / immunology*
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Hematopoietic Stem Cells / metabolism*
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Hematopoietic Stem Cells / radiation effects
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / radiation effects
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Histocompatibility Antigens Class II / biosynthesis*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / radiation effects
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Interferon-gamma / biosynthesis
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / radiation effects
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Lymphocyte Subsets / immunology
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Lymphocyte Subsets / metabolism
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Lymphocyte Subsets / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Radiation Chimera / genetics
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Radiation Chimera / immunology*
Substances
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Interferon-gamma