Visualization of the human CD4(+) T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/gammac(null) (NOG) mice by retrogenic expression of the human TCR gene
Visualization of the human CD4(+) T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/gammac(null) (NOG) mice by retrogenic expression of the human TCR gene
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通过人 TCR 基因的逆转录表达，对表达 HLA-DR4 的人源化 NOD/Shi-scid/gammac(null) (NOG) 小鼠中的人 CD4( ) T 细胞反应进行可视化
DOI：
10.1016/j.bbrc.2014.11.062
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Takahashi;T. Katano;I. Ito;R. Ito;M.
含有细胞因子或 HLA 等多种人类基因的严重免疫缺陷小鼠品系的开发，使得在移植人类造血干细胞 (HSC) 后能够重建功能性人类免疫系统。越来越多的证据表明，这些人源化小鼠可以产生 HLA 限制性抗原特异性人类 T 细胞反应。为了直接监测人类 CD4+T 细胞的免疫反应，我们将源自牛奶过敏患者 CD4+T 细胞克隆的 β-乳球蛋白 (BLG) 特异性 T 细胞受体 (TCR) 基因引入到 HSC 中，随后将其移植到 NOG-HLA-DR4 转基因/I-Aβ 缺陷小鼠 (NOG-DR4/I-Ao) 中。在胸腺中，具有 BLG 特异性 TCR 的胸腺细胞优先分化为 CD4+CD8−单阳性细胞。将表达 TCR 的成熟 CD4+T 细胞过继转移到受体 NOG-DR4/I-Aomice 中，证明人 CD4+T 细胞响应抗原刺激而增殖，并在体内产生 IFN-γ，这表明在人源化小鼠中诱导了功能性 T 细胞反应（尤其是 Th1 偏向反应）。
The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4+T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4+T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-Ao). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4+CD8−single-positive cells. Adoptive transfer of mature CD4+T cells expressing the TCR into recipient NOG-DR4/I-Aomice demonstrated that human CD4+T cells proliferated in response to antigenic stimulation and produced IFN-γin vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.