期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 12, 页码 6002-6009出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301212
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资金
- INSERM
- Institut Curie
- Agence Nationale de la Recherche (Blanc and Labex Project Biologie des Cellules Dendritique)
- Fondation Aupetit
- Equipe Labellisee de la Ligue Contre le Cancer
- Fondation Association pour la Recherche sur le Cancer
- Fondation pour la Recherche Medicale
- European Molecular Biology Organization
- Cancer Research Institute/Irvington Lloyd J. Old Fellowship in Tumor Immunology
- Fondation de la Recherche Medicale
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 iV alpha 19 transgenic and V beta 6 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.
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