Abstract
The nonclassical MHC class I molecule MHC class I-related chain A (MICA) interacts with the NKG2D receptor expressed at the surface of most peripheral CD8 T cells, gammadelta T cells, and NK cells. We investigated the role of MICA-NKG2D interactions in the selection or maturation of the T cell repertoire within the thymus using MICA tetramers and anti-MICA mAbs. MICA tetramers identified a small population of late stage CD8 single-positive, CD45RA(+) CD62L(+) CCR7(+) CD69(-) thymocytes, a phenotype compatible with that of fully mature CD8(+) cells ready to emigrate to the periphery as naive cells. MICA molecules were expressed in the outer layer of Hassal's corpuscles within the medulla of normal thymus. In thymomas, an overexpression of MICA in cortical and medullar epithelial cells was observed. This was associated with a decreased percentage of NKG2D-positive thymocytes, which expressed a less mature phenotype than in normal thymus. These results indicate that CD8(+) thymocytes up-regulate NKG2D as they complete their developmental program before leaving the thymic medulla to seed the periphery, and identify NKG2D as a potential regulator of the developmental processes in T cells that are essential for immune homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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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 / immunology
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Cells, Cultured
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Child
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Child, Preschool
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HT29 Cells
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HeLa Cells
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / blood
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Histocompatibility Antigens Class I / metabolism
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Histocompatibility Antigens Class I / physiology*
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Humans
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Immunophenotyping
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Infant
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Infant, Newborn
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Lymphocyte Subsets / immunology
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Lymphocyte Subsets / metabolism
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NK Cell Lectin-Like Receptor Subfamily K
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Neoplasms, Glandular and Epithelial / immunology
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Neoplasms, Glandular and Epithelial / metabolism
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Neoplasms, Glandular and Epithelial / pathology
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Protein Binding / immunology
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / metabolism
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Receptors, Immunologic / physiology*
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Receptors, Natural Killer Cell
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Thymoma / immunology
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Thymoma / pathology
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Thymus Gland / cytology*
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Thymus Gland / immunology
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Thymus Gland / metabolism*
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Thymus Gland / pathology
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Thymus Neoplasms / immunology
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Thymus Neoplasms / pathology
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Tumor Cells, Cultured
Substances
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Histocompatibility Antigens Class I
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KLRK1 protein, human
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MHC class I-related chain A
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MICB antigen
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NK Cell Lectin-Like Receptor Subfamily K
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Receptors, Immunologic
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Receptors, Natural Killer Cell