Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model
Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model
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DOI：
10.1182/blood-2007-11-121319
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发表时间：
2008-04-15
期刊：
影响因子：
20.3
通讯作者：
Yang, Yong-Guang
中科院分区：
文献类型：
--
作者：
Tonomura, Noriko;Habiro, Katsuyoshi;Yang, Yong-Guang
具有人类免疫系统功能的人源化小鼠将对人体免疫生物学的活体研究非常有用。我们已经证明，将人胎胸腺/肝组织和CD34(+)胎肝细胞共移植到免疫缺陷的非肥胖糖尿病严重联合免疫缺陷(NOD/SCID)小鼠体内，可以导致人类淋巴造血细胞的多个谱系的发育，并形成具有正常结构的次级淋巴器官。在这里，我们评估了这些人源化小鼠在T依赖抗原2，4-二硝基苯半抗原-锁孔帽状血蓝蛋白(DNP23-KLH)体内免疫后产生抗原特异性T细胞依赖性抗体反应的能力。DNP23-KLH免疫的小鼠的人T细胞在体外对KLH有较强的增殖反应。此外，在所有免疫小鼠中都检测到依赖T细胞产生的DNP特异性人类抗体(主要是IgG1和IgG2)。这些结果证实，通过人胎胸腺/肝组织和CD34(+)造血干/祖细胞的共移植，可以在免疫缺陷小鼠中建立起功能正常的人类免疫系统。
Humanized mice with a functional human immune system would be very useful for in vivo studies of human immunobiology. We have previously shown that cotransplantation of human fetal thymus/liver tissues and CD34(+) fetal liver cells into immunodeficient nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice leads to the development of multiple lineages of human lymphohematopoietic cells and formation of secondary lymphoid organs with normal architecture. Here, we evaluated the ability of these humanized mice to develop antigen-specific, T cell-dependent antibody responses after in vivo immunization with T-dependent antigen, 2,4-dinitrophenyl hapten-keyhole limpet hemocyanin (DNP23-KLH). Human T cells from DNP23-KLH-immunized mice showed strong proliferation in response to KLH in vitro. Furthermore, T cell-dependent production of DNP-specific human antibodies (mainly IgG1 and IgG2) was detected in all immunized mice. These results confirm that a functional human immune system can be established in immunodeficient mice through cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells.