Abstract
Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in host mucosal immunity and, unlike other T cells, have been proposed to differentiate from local precursors rather than from thymocytes. We show here that IELs expressing the alphabeta T cell receptor are derived from precursors that express RORgammat, an orphan nuclear hormone receptor detected only in immature CD4+CD8+ thymocytes, fetal lymphoid tissue-inducer (LTi) cells, and LTi-like cells in cryptopatches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal alphabeta T cells are progeny of CD4+CD8+ thymocytes, indicating that the adult intestine is not a significant site for alphabeta T cell development. Our results suggest that intestinal RORgammat+ cells are local organizers of mucosal lymphoid tissue.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4 Antigens / analysis
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CD8 Antigens / analysis
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Cell Lineage
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DNA-Binding Proteins / metabolism
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Hematopoietic Stem Cells / immunology
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Hematopoietic Stem Cells / physiology
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Immunity, Mucosal
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology*
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Lymphoid Tissue / embryology
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Lymphoid Tissue / immunology
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Mice
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Mice, Transgenic
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell, alpha-beta / analysis*
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / analysis
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism*
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / metabolism*
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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Thymus Gland / cytology
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Thymus Gland / immunology*
Substances
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CD4 Antigens
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CD8 Antigens
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DNA-Binding Proteins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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V(D)J recombination activating protein 2