Double Positive Thymocytes Select Mucosal-Associated Invariant T Cells
Double Positive Thymocytes Select Mucosal-Associated Invariant T Cells
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DOI：
10.4049/jimmunol.1301212
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发表时间：
2013-12
期刊：
影响因子：
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通讯作者：
N. Seach;L. Guerri;L. Le Bourhis;Yvonne K. Mburu;Yue Cui;Stéphanie Bessoles;C. Soudais;O. Lantz
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文献类型：
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作者：
N. Seach;L. Guerri;L. Le Bourhis;Yvonne K. Mburu;Yue Cui;Stéphanie Bessoles;C. Soudais;O. Lantz
NKT和粘膜相关不变T（MAIT）细胞表达半不变TCR和非经典MHC Ib类分子的限制。尽管有共同的特点，NKT和MAIT亚群各自的发展是不同的。NKT广泛增殖并在胸腺输出之前获得效应子特性。MAIT细胞作为幼稚细胞离开胸腺，并在需要体内植物群和B细胞的过程中获得效应/记忆表型。在胸腺发育过程中，NKT被表达CD 1d的皮质胸腺细胞选择;然而，负责MAIT细胞选择的造血细胞类型仍未得到解决。使用再聚集的胸腺器官培养和骨髓嵌合体，我们证明小鼠iVα19转基因和Vβ6转基因MAIT细胞祖细胞的阳性选择需要MHC相关1表达的CD 4 + CD 8+双阳性胸腺细胞，而胸腺B细胞、巨噬细胞和树突状细胞亚群是不稳定的。双阳性胸腺细胞与外源性细菌配体预孵育增加MHC相关1表面表达，并增强体外共培养中成熟MAIT细胞的活化。一个共同的细胞类型的选择NKT和MAIT子集的启示提出了关于其特定功能的收购机制的问题。
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.