Abstract
NKT and mucosal-associated invariant T (MAIT) cells express semi-invariant TCR and restriction by nonclassical MHC class Ib molecules. Despite common features, the respective development of NKT and MAIT subsets is distinct. NKTs proliferate extensively and acquire effector properties prior to thymic export. MAIT cells exit the thymus as naive cells and acquire an effector/memory phenotype in a process requiring both commensal flora and B cells. During thymic development, NKTs are selected by CD1d-expressing cortical thymocytes; however, the hematopoietic cell type responsible for MAIT cell selection remains unresolved. Using reaggregated thymic organ culture and bone marrow chimeras, we demonstrate that positive selection of mouse iVα19 transgenic and Vβ6 transgenic MAIT cell progenitors requires MHC-related 1-expressing CD4(+)CD8(+) double positive thymocytes, whereas thymic B cells, macrophages, and dendritic cell subsets are dispensable. Preincubation of double positive thymocytes with exogenous bacterial ligand increases MHC-related 1 surface expression and enhances mature MAIT cell activation in the in vitro cocultures. The revelation of a common cell type for the selection of both NKT and MAIT subsets raises questions about the mechanisms underlying acquisition of their specific features.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation
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Antigens, Bacterial / immunology
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Antigens, Differentiation, T-Lymphocyte / analysis
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CD4 Antigens / analysis*
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CD8 Antigens / analysis*
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Cell Lineage
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Cells, Cultured
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Clonal Selection, Antigen-Mediated*
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Coculture Techniques
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Escherichia coli / immunology
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Female
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Genes, Immunoglobulin
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Hematopoietic Stem Cells / classification
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Hematopoietic Stem Cells / cytology
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology*
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Immunoglobulin Variable Region / genetics
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Immunologic Deficiency Syndromes / genetics
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Immunologic Deficiency Syndromes / immunology
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Lymphocyte Activation
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Lymphopoiesis / immunology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Natural Killer T-Cells / cytology
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Natural Killer T-Cells / immunology
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Organ Culture Techniques
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Radiation Chimera
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Specific Pathogen-Free Organisms
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Stromal Cells / physiology
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T-Lymphocyte Subsets / chemistry
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T-Lymphocyte Subsets / immunology*
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Thymus Gland / cytology
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Thymus Gland / immunology
Substances
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Antigens, Bacterial
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Antigens, Differentiation, T-Lymphocyte
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CD4 Antigens
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CD8 Antigens
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Histocompatibility Antigens Class I
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Immunoglobulin Variable Region
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Minor Histocompatibility Antigens
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Mr1 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta