Wang Yong, Zhang Yanyun, Yoneyama Hiroyuki, Onai Nobuyuki, Sato Taku, Matsushima Kouji
Department of Molecular Preventive Medicine and CREST, School of Medicine, The University of Tokyo, Tokyo, Japan.
Blood. 2002 Jul 15;100(2):569-77. doi: 10.1182/blood.v100.2.569.
CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cells could differentiate into CD8alpha+ DCs in vivo after intravenous transplantation. Immunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas of the spleen. Functionally, these CD8alpha+CD11c-Lin- cell-derived DCs were capable of stimulating allogenic T-cell response, as well as secreting bioactive interleukin 12 p70 and interferon gamma. Freshly isolated CD8alpha+CD11c-Lin- cells expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA, whereas CD8alpha+ DCs derived from CD8alpha+CD11c-Lin- cells further obtained the expression of CCR6 and macrophage-derived chemokine. Flow cytometry analysis showed that CD8alpha+CD11c-Lin- cells were identified in bone marrow and lymph nodes. Moreover, transplanted splenic CD8alpha+CD11c-Lin- cells could also home to thymus and lymph nodes and were capable of developing into CD8alpha+ DCs in these locations. However, CD8alpha+CD11c-Li- cells failed to differentiate into CD8alpha- DCs, T cells, natural killer cells, or other myeloid lineage cells in irradiated chimeras. Taken together, all these findings suggest that CD8alpha+CD11c-Lin- cells are a committed precursor of CD8alpha+ DCs.
CD8α⁺树突状细胞（DCs）在体内代表一个功能独特的DC亚群，在启动各种细胞免疫反应中起关键作用。然而，CD8α⁺DCs的定向前体仍有待确定。我们在此报告，小鼠脾脏CD8α⁺CD11c⁻谱系表型（Lin）⁻细胞经静脉移植后可在体内分化为CD8α⁺DCs。免疫组织化学染色显示，供体来源的DCs主要位于脾脏的T细胞区。在功能上，这些CD8α⁺CD11c⁻Lin⁻细胞来源的DCs能够刺激同种异体T细胞反应，以及分泌生物活性白细胞介素12 p70和干扰素γ。新鲜分离的CD8α⁺CD11c⁻Lin⁻细胞表达CC趋化因子受体（CCR）2、CCR5和CCR7信使核糖核酸，而源自CD8α⁺CD11c⁻Lin⁻细胞的CD8α⁺DCs进一步获得了CCR6和巨噬细胞衍生趋化因子的表达。流式细胞术分析显示，在骨髓和淋巴结中可鉴定出CD8α⁺CD11c⁻Lin⁻细胞。此外，移植的脾脏CD8α⁺CD11c⁻Lin⁻细胞也可归巢至胸腺和淋巴结，并能够在这些部位发育为CD8α⁺DCs。然而，在受照射的嵌合体中，CD8α⁺CD11c⁻Li⁻细胞未能分化为CD8α⁻DCs、T细胞、自然杀伤细胞或其他髓系谱系细胞。综上所述，所有这些发现表明CD8α⁺CD11c⁻Lin⁻细胞是CD8α⁺DCs的定向前体。
