Abstract
A major pathogenic factor for the development of inflammatory bowel disease (IBD) is the breakdown of the intestinal homeostasis between the host immune system and the luminal microenvironment. To assess the potential influence of luminal Ags on the development of IBD, we fed TCR alpha(-/-) mice an elemental diet (ED). ED-fed TCR alpha(-/-) mice showed no pathologic features of IBD, and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4(+), TCR betabeta homodimer T cells (betabeta T cells) were developed in the colonic mucosa of ED-fed mice; however, Th2-type cytokine productions were lower than those seen in diseased regular diet (RD)-fed mice. The higher cytokine production in diseased RD-fed mice could be attributed to the high incidence of Bacteroides vulgatus (recovered in 80% of these mice), which can induce Th2-type responses of colonic CD4(+), betabeta T cells. In contrast, ED-fed TCR alpha(-/-) mice exhibited a diversification of Vbeta usage of betabetaT cell populations from the dominant Vbeta8 one associated with B. vulgatus in cecal flora to Vbeta6, Vbeta11, and Vbeta14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4(+), betabeta T cell-induced colitis. These findings suggest that the ED-induced alteration of intestinal microenvironments such as the enteric flora prevented the development of IBD in TCR alpha(-/-) mice via the immunologic quiescence of CD4(+), betabeta T cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Rectal
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Animals
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Antibody-Producing Cells / pathology
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Bacteroides / growth & development
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Bacteroides / immunology
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Bacteroides Infections / genetics
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Bacteroides Infections / immunology
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Bacteroides Infections / prevention & control*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / microbiology
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CD4-Positive T-Lymphocytes / pathology
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Cecum / microbiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Cells, Cultured
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Coculture Techniques
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Colitis / genetics
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Colitis / immunology
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Colitis / prevention & control*
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Colon / immunology
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Colon / metabolism
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Colon / microbiology
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Cytokines / antagonists & inhibitors
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Cytokines / biosynthesis*
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Dimerization
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Food, Formulated
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Immune Tolerance / genetics
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Intestinal Mucosa / immunology
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Intestinal Mucosa / microbiology
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Intestinal Mucosa / pathology
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Leukocyte Count
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Spleen / immunology
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Spleen / metabolism
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Spleen / microbiology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / microbiology
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T-Lymphocyte Subsets / pathology
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Cytokines
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Receptors, Antigen, T-Cell, alpha-beta