T Lymphocyte Development and Activation in Humanized Mouse Model.
T Lymphocyte Development and Activation in Humanized Mouse Model.
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DOI：
10.12717/dr.2019.23.2.079
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发表时间：
2019-06-01
期刊：
影响因子：
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通讯作者：
Lee, Dong Ryul
中科院分区：
文献类型：
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作者：
Lee, Ji Yoon;Han, A-Reum;Lee, Dong Ryul
含有移植的人类细胞和组织的人源化小鼠正在成为研究人类疾病的重要体内平台。自从IL-2受体γ链突变的Nod scid gamma（NSG）小鼠出现以来，许多研究者使用移植有人造血干细胞（HSC）的NSG小鼠在体内产生功能性人免疫系统，导致人细胞移植的高效率。NSG小鼠的发展使得对几种人类疾病的研究取得了重大进展，包括癌症和移植物抗宿主病（GVHD）以及再生医学。在人造血干细胞移植的基础上，进行了包括胸腺和肝脏在内的肾包膜内器官移植。此外，淋巴细胞和髓系细胞的免疫重建也已部分完成。然而，具有人白细胞抗原（HLA）错配/匹配类型的多能干细胞衍生的治疗性细胞与免疫CD 3 T细胞之间的串扰尚未完全解决。为了克服这一障碍，需要人类主要组织相容性复合体（MHC）分子，而不是小鼠MHC分子，在人源化小鼠模型中产生功能性T细胞。在这里，我们简要地总结了人源化小鼠模型的特点，重点是CD 3 T细胞与MHC分子的发展。我们还强调了人源化小鼠模型用于治疗各种人类疾病的必要性。
Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.