The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system.
The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system.
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DOI：
10.1084/jem.177.3.821
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发表时间：
1993-03-01
期刊：
影响因子：
--
通讯作者：
Goldstein H
中科院分区：
文献类型：
--
作者：
Kollmann TR;Goldstein MM;Goldstein H
为了确定人胸腺是否为鼠T细胞的成熟提供环境，将人胎儿胸腺和肝（hu-thy/liv）植入先天无胸腺NIH-米色-裸-xid（BNX）小鼠或C.B-17 scid/scid（SCID）小鼠中。植入后3个月，与SCID小鼠中的hu-thy/liv植入物（仅填充人CD 4/CD 8单阳性和双阳性胸腺细胞）相反，BNX小鼠中的hu-thy/liv植入物包含人和小鼠CD 4/CD 8单阳性和双阳性胸腺细胞的嵌合群体。BNX小鼠中hu-thy/liv植入物的免疫组织化学染色表明，双阳性小鼠胸腺细胞群体定位于人胎胸腺的离散区域。将人胎胸腺和肝组织移植入BNX小鼠后，观察到小鼠T细胞和免疫球蛋白（IG）G参数的定量改善。此外，与未植入的BNX小鼠相反，植入的BNX小鼠能够产生匙孔血蓝蛋白特异性IgG反应，其外周T细胞对针对T细胞受体的有丝分裂原和抗体的刺激有反应。此外，在体内致敏后，植入BNX小鼠淋巴结中存在的T细胞能够产生抗原诱导的体外T细胞依赖性增殖反应。因此，在人T细胞持续成熟的同时，鼠T细胞在植入BNX小鼠的人胎胸腺内分化，并介导鼠免疫系统的表型和功能重建。含有可感染人类免疫缺陷病毒（HIV）的人胸腺植入物的重建免疫系统的小鼠应证明可用于胸腺中T细胞成熟的研究和潜在HIV疫苗的评价。
To determine whether the human thymus provides an environment for the maturation of murine T cells, human fetal thymus and liver (hu-thy/liv) were implanted into congenitally athymic NIH-beige-nude-xid (BNX) mice or C.B-17 scid/scid (SCID) mice. 3 mo after implantation, in contrast to the hu-thy/liv implant in SCID mice, which was populated only with human CD4/CD8 single- and double-positive thymocytes, the hu-thy/liv implant in BNX mice contained a chimeric population of human and mouse CD4/CD8 single- and double-positive thymocytes. Immunohistochemical staining of the hu-thy/liv implant in BNX mice indicated that the population of double-positive mouse thymocytes was localized to discrete areas of the human fetal thymus. Quantitative improvements in mouse T cell and immunoglobulin (Ig) G parameters were observed after grafting of the human fetal thymus and liver tissue into BNX mice. In addition, in contrast to the nonimplanted BNX mice, the implanted BNX mice were capable of mounting a keyhole limpet hemocyanin-specific IgG response and their peripheral T cells were responsive to stimulation with mitogens and antibodies directed to the T cell receptor. Furthermore, after in vivo priming, T cells present in lymph nodes of the implanted BNX mice were capable of mounting an antigen-induced in vitro T cell-dependent proliferative response. Thus, concurrent with the continued maturation of human T cells, murine T cells differentiated within the human fetal thymus implanted in the BNX mice and mediated the phenotypic and functional reconstitution of the murine immune system. Mice with a reconstituted immune system that contain a human thymic implant that is infectible with human immunodeficiency virus (HIV) should prove useful in the investigation of T cell maturation in the thymus and in the evaluation of potential HIV vaccines.