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Functional Human CD141+ Dendritic Cells in Human Immune System Mice.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-02 , DOI: 10.1093/infdis/jiz432
Jordana G A Coelho-Dos-Reis 1, 2 , Ryota Funakoshi 1 , Jing Huang 1 , Felipe Valença Pereira 1, 3 , Sho Iketani 1, 4 , Moriya Tsuji 1
Affiliation  

BACKGROUND For the purpose of studying functional human dendritic cells (DCs) in a humanized mouse model that mimics the human immune system (HIS), a model referred to as HIS mice was established. METHODS Human immune system mice were made by engrafting NOD/SCID/IL2Rgammanull (NSG) mice with human hematopoietic stem cells (HSCs) following the transduction of genes encoding human cytokines and human leukocyte antigen (HLA)-A2.1 by adeno-associated virus serotype 9 (AAV9) vectors. RESULTS Our results indicate that human DC subsets, such as CD141+CD11c+ and CD1c+CD11c+ myeloid DCs, distribute throughout several organs in HIS mice including blood, bone marrow, spleen, and draining lymph nodes. The CD141+CD11c+ and CD1c+CD11c+ human DCs isolated from HIS mice immunized with adenoviruses expressing malaria/human immunodeficiency virus (HIV) epitopes were able to induce the proliferation of malaria/HIV epitopes-specific human CD8+ T cells in vitro. Upregulation of CD1c was also observed in human CD141+ DCs 1 day after immunization with the adenovirus-based vaccines. CONCLUSIONS Establishment of such a humanized mouse model that mounts functional human DCs enables preclinical assessment of the immunogenicity of human vaccines in vivo.

中文翻译:

人免疫系统小鼠中的功能性人CD141 +树突状细胞。

背景技术出于在模拟人免疫系统(HIS)的人源化小鼠模型中研究功能性人树突细胞(DC)的目的,建立了称为HIS小鼠的模型。方法通过在腺相关病毒转导编码人细胞因子和人白细胞抗原(HLA)-A2.1的基因后,通过向NOD / SCID / IL2Rgammanull(NSG)小鼠植入人造血干细胞(HSC)制备人免疫系统小鼠血清型9(AAV9)载体。结果我们的结果表明,人DC子集,例如CD141 + CD11c +和CD1c + CD11c +髓样DC,分布在HIS小鼠的多个器官中,包括血液,骨髓,脾脏和引流淋巴结。从表达疟疾/人免疫缺陷病毒(HIV)表位的腺病毒免疫的HIS小鼠中分离出的CD141 + CD11c +和CD1c + CD11c +人DC能够在体外诱导疟疾/ HIV表位特异性的人CD8 + T细胞的增殖。用基于腺病毒的疫苗免疫后1天,在人CD141 + DC中也观察到CD1c的上调。结论建立具有功能性人DC的人源化小鼠模型,可以对人疫苗在体内的免疫原性进行临床前评估。
更新日期:2019-12-30
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