Abstract
CD1d-restricted autoreactive natural killer (NK1.1+) T cells function as regulatory cells in various disease conditions. Using improved tetramer tracking methodology, we identified a NK1.1- thymic precursor and followed its differentiation and emigration to tissues by direct cell transfer and in situ cell labeling studies. A major lineage expansion occurred within the thymus after positive selection and before NK receptor expression. Surprisingly, cytokine analysis of the developmental intermediates between NK and NK+ stages showed a T helper cell TH2 to TH1 conversion, suggesting that the regulatory functions of NK T cells may be developmentally controlled. These findings characterize novel thymic and postthymic developmental pathways that expand autoreactive cells and differentiate them into regulatory cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens / analysis
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Antigens, CD1 / analysis
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Antigens, CD1 / immunology
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Antigens, CD1d
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Antigens, Ly
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Antigens, Surface
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Cell Differentiation
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Cell Division
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Cell Lineage*
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Hyaluronan Receptors / analysis
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Interferon-gamma / biosynthesis
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Interleukins / biosynthesis
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology*
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Lectins, C-Type
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Liver / cytology
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Liver / immunology
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Lymphocyte Activation
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Mice
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NK Cell Lectin-Like Receptor Subfamily B
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Proteins / analysis
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Receptors, Antigen, T-Cell, alpha-beta / analysis
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Immunologic / analysis
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Receptors, Immunologic / immunology
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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Thymus Gland / cytology*
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Thymus Gland / immunology
Substances
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Antigens
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Antigens, CD1
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Antigens, CD1d
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Antigens, Ly
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Antigens, Surface
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Hyaluronan Receptors
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Interleukins
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Klrb1c protein, mouse
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily B
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Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Immunologic
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Interferon-gamma