Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Transpl Immunol. 2011 Dec;25(4):173-9. doi: 10.1016/j.trim.2011.08.003. Epub 2011 Aug 11.
Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical regulators of immune tolerance in humans and mice. Mice with humanized immunity have been developed by various transplantation strategies of human tissues or cells related to immunity, which are being extensively applied in biomedical research. However, it is unclear whether human CD4(+)CD25(+) regulatory T cells can normally develop in human thymic grafts and efficiently populate in the periphery in NOD/SCID mouse recipients. In human thymic grafts, high percentage of mature human CD4(+)CD25(high) regulatory T cells was detected. Human CD4(+)CD25(+) regulatory T cells maturing in fetal human thymus grafts could subsequently output to the periphery of NOD/SCID mouse recipients. Importantly, these cells exhibited Foxp3(+)CD45RO(+)CTLA4(+)CD127(-) phenotype, similarly to those in healthy individuals. In addition, human CD4(+)CD25(+) regulatory T cells maturing in human thymic grafts suppressed proliferative response of CD4(+)CD25(-) T cells to allogeneic antigens, though the peripheral CD4(+)CD25(+) regulatory T cells in fetal human thymus-grafted NOD/SCID mice showed somewhat decreased immunosuppressive ability compared with normal CD4(+)CD25(+) regulatory T cells. Thus, this humanized animal model is suitable for examining development and function of human CD4(+)CD25(+) regulatory T cells in vivo.
调节性 T 细胞，尤其是 CD4(+)CD25(+)调节性 T 细胞，是人类和小鼠免疫耐受的关键调节因子。通过各种与免疫相关的人类组织或细胞的移植策略，已经开发出具有人类化免疫的小鼠，这些小鼠正在广泛应用于生物医学研究中。然而，目前尚不清楚人类 CD4(+)CD25(+)调节性 T 细胞是否能在人类胸腺移植物中正常发育，并在 NOD/SCID 小鼠受体内有效地定植到外周。在人类胸腺移植物中，检测到成熟的人类 CD4(+)CD25(high)调节性 T 细胞的比例较高。在胎牛胸腺移植物中成熟的人类 CD4(+)CD25(+)调节性 T 细胞随后可以输出到 NOD/SCID 小鼠受体内的外周。重要的是，这些细胞表现出 Foxp3(+)CD45RO(+)CTLA4(+)CD127(-)表型，与健康个体中的细胞相似。此外，在人类胸腺移植物中成熟的人类 CD4(+)CD25(+)调节性 T 细胞抑制 CD4(+)CD25(-)T 细胞对同种异体抗原的增殖反应，尽管胎牛胸腺移植的 NOD/SCID 小鼠中的外周 CD4(+)CD25(+)调节性 T 细胞的免疫抑制能力与正常的 CD4(+)CD25(+)调节性 T 细胞相比有所降低。因此，这种人类化动物模型适合用于体内研究人类 CD4(+)CD25(+)调节性 T 细胞的发育和功能。
