Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
J Immunol. 2011 Jun 1;186(11):6207-17. doi: 10.4049/jimmunol.1002632. Epub 2011 Apr 22.
Mouse dendritic cells (DC) have been extensively studied in various tissues, especially spleen, and they comprise subsets with distinct developmental origins, surface phenotypes, and functions. Considerably less is known about human DC due to their rarity in blood and inaccessibility of other human tissues. The study of DC in human blood has revealed four subsets distinct in phenotype and function. In this study, we describe four equivalent DC subsets in human spleen obtained from deceased organ donors. We identify three conventional DC subsets characterized by surface expression of CD1b/c, CD141, and CD16, and one plasmacytoid DC subset characterized by CD304 expression. Human DC subsets in spleen were very similar to those in human blood with respect to surface phenotype, TLR and transcription factor expression, capacity to stimulate T cells, cytokine secretion, and cross-presentation of exogenous Ag. However, organ donor health status, in particular treatment with corticosteroid methylprednisolone and brain death, may affect DC phenotype and function. DC T cell stimulatory capacity was reduced but DC were qualitatively unchanged in methylprednisolone-treated deceased organ donor spleen compared with healthy donor blood. Overall, our findings indicate that human blood DC closely resemble human spleen DC. Furthermore, we confirm parallels between human and mouse DC subsets in phenotype and function, but also identify differences in transcription factor and TLR expression as well as functional properties. In particular, the hallmark functions of mouse CD8α(+) DC subsets, that is, IL-12p70 secretion and cross-presentation, are not confined to the equivalent human CD141(+) DC but are shared by CD1b/c(+) and CD16(+) DC subsets.
小鼠树突状细胞 (DC) 在各种组织中得到了广泛研究，尤其是在脾脏中，它们包括具有不同发育起源、表面表型和功能的亚群。由于人 DC 在血液中稀少且其他人体组织难以获取，因此对其了解甚少。对人血液中的 DC 的研究揭示了在表型和功能上明显不同的四个亚群。在这项研究中，我们描述了从已故器官供体中获得的人脾脏中的四个等效的 DC 亚群。我们鉴定了三个具有 CD1b/c、CD141 和 CD16 表面表达特征的常规 DC 亚群，以及一个具有 CD304 表达特征的浆细胞样 DC 亚群。人脾脏中的 DC 亚群在表面表型、TLR 和转录因子表达、刺激 T 细胞的能力、细胞因子分泌和外源性 Ag 的交叉呈递方面与血液中的 DC 非常相似。然而，器官供体的健康状况，特别是皮质类固醇甲泼尼龙的治疗和脑死亡，可能会影响 DC 的表型和功能。与健康供体血液相比，接受甲泼尼龙治疗的已故器官供体脾脏中的 DC 刺激 T 细胞的能力降低，但 DC 的表型未发生变化。总体而言，我们的研究结果表明，人血液中的 DC 与人脾脏中的 DC 非常相似。此外，我们证实了人 DC 亚群和鼠 DC 亚群在表型和功能上存在相似之处，但也发现了转录因子和 TLR 表达以及功能特性方面的差异。特别是，鼠 CD8α(+) DC 亚群的标志性功能，即 IL-12p70 的分泌和交叉呈递，不仅局限于等效的人 CD141(+) DC，而且还由 CD1b/c(+) 和 CD16(+) DC 亚群共享。
