Abstract
Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, T-Independent / immunology*
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Bone Marrow Transplantation
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Lineage / genetics
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Cell Lineage / immunology
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Dimerization
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Intestinal Mucosa / cytology*
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / metabolism
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Proto-Oncogene Proteins c-kit / biosynthesis
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Radiation Chimera / immunology
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Receptor, Notch1
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Receptors, Cell Surface*
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Transcription Factors*
Substances
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Antigens, T-Independent
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Membrane Proteins
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Notch1 protein, mouse
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Receptor, Notch1
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Receptors, Cell Surface
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Transcription Factors
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Proto-Oncogene Proteins c-kit