CD11c+ MHCIIlo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma
CD11c+ MHCIIlo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma
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DOI：
10.1007/s00262-018-2202-4
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发表时间：
2018-09-01
影响因子：
5.8
通讯作者：
Srivastava, Pramod K.
中科院分区：
文献类型：
--
作者：
Ebrahimi-Nik, Hakimeh;Corwin, William L.;Srivastava, Pramod K.
树突状细胞在启动T细胞应答中起关键作用。尽管认识到这一点，但它们还没有被广泛用作佐剂，它们的佐剂性机制也没有完全理解。在这里，使用小鼠纤维肉瘤的突变的新表位作为抗原，肿瘤排斥作为终点，我们表明树突状细胞而不是巨噬细胞具有上级的佐剂性。几种类型的树突状细胞，如骨髓来源的树突状细胞（GM-CSF培养的或FLT 3-配体诱导的）或单核细胞来源的树突状细胞，是强有力的佐剂，尽管GM-CSF培养的细胞显示出最高的活性。其中，CD 11 c（+）MHCIIlo亚组通过包括热休克蛋白受体CD 91和LOX 1、甘露糖受体和TLR的较高表达的独特转录谱而可区分，其显著上级于CD 11 c（+）MHCIIhi亚组。最后，树突细胞通过充当抗原供体细胞（即，抗原储库）以及抗原呈递细胞。
Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c(+) MHCIIlo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c(+) MHCIIhi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.