Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, England, UK.
J Exp Med. 2011 Feb 14;208(2):227-34. doi: 10.1084/jem.20101459. Epub 2011 Jan 17.
Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR(+) lineage(-) compartment, with virtually no CD123(+) or CD11c(+) dendritic cells (DCs) and very few CD14(+) or CD16(+) monocytes. The only remaining HLA-DR(+) lineage(-) cells were circulating CD34(+) progenitor cells. Dermal CD14(+) and CD1a(+) DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR(+) peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4(+)CD25(hi)FoxP3(+) T cells, supporting a role for DC in T reg cell homeostasis.
人类先天性或获得性的细胞缺陷有可能揭示正常造血和免疫功能的许多信息。我们表明，最近描述的单核细胞减少症、B 和 NK 淋巴样缺陷综合征还包括树突状细胞（DC）的几乎缺失。四名受试者的外周血 HLA-DR(+)谱系(-) 细胞严重耗竭，几乎没有 CD123(+)或 CD11c(+)树突状细胞（DC），CD14(+)或 CD16(+)单核细胞也非常少。唯一剩下的 HLA-DR(+)谱系(-)细胞是循环 CD34(+)祖细胞。真皮 CD14(+)和 CD1a(+) DC 也不存在，这与其对血液来源前体的依赖性一致。相比之下，表皮朗格汉斯细胞和组织巨噬细胞基本得以保留。外周 DC、单核细胞、B 和 NK 淋巴细胞的联合缺失在骨髓中表现为多淋巴样祖细胞完全缺失和粒细胞-巨噬细胞祖细胞耗竭。外周血 HLA-DR(+) 细胞群的耗竭与血清 fms 样酪氨酸激酶配体升高和循环 CD4(+)CD25(hi)FoxP3(+)T 细胞减少有关，支持 DC 在 Treg 细胞稳态中的作用。
