Saito Yuki, Kametani Yoshie, Hozumi Katsuto, Mochida Naoko, Ando Kiyoshi, Ito Mamoru, Nomura Tatsuji, Tokuda Yutaka, Makuuchi Hiroyasu, Tajima Tomoo, Habu Sonoko
Department of Immunology, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
Int Immunol. 2002 Oct;14(10):1113-24. doi: 10.1093/intimm/dxf087.
There is increasing evidence that human hematopoietic stem cells can develop into lymphocytes expressing T cell surface markers in the organ culture of murine embryonic thymic lobes. If human T cells with functional maturity are inducible from human stem cells in the mouse, it may be a useful model to investigate human T cell development and the human immune response in vivo. To approach this, we produced a hybrid cluster of murine fetal thymic epithelial cells and human cord blood-derived CD34(+) cells (hu/m cluster) using reaggregate thymic organ culture, and subsequently implanted it under the kidney capsule of NOD/SCID mice. The implanted hu/m cluster grew in volume under the kidney capsule and contained increased numbers of CD4(+)CD8(+)cells as well as CD4 or CD8 single-positive cells with low CD1a expression. These lymphocytes were also shown to possess activity for producing IL-2 and IL-4. Characteristics similar to human T cells also developed in the thymus of newly established mice lacking NK activity from NOD/SCID mice. These results indicate that functionally mature T cells can develop in vivo from human hematopoietic progenitors in the murine environment composed of thymic epithelial cells.
越来越多的证据表明，在小鼠胚胎胸腺叶的器官培养中，人类造血干细胞可以发育成表达T细胞表面标志物的淋巴细胞。如果在小鼠体内能从人类干细胞诱导出功能成熟的人类T细胞，那么它可能是一个在体内研究人类T细胞发育和人类免疫反应的有用模型。为了实现这一点，我们使用重组胸腺器官培养法制备了小鼠胎儿胸腺上皮细胞和人类脐带血来源的CD34(+)细胞的混合簇（hu/m簇），随后将其植入NOD/SCID小鼠的肾包膜下。植入的hu/m簇在肾包膜下体积增大，含有数量增加的CD4(+)CD8(+)细胞以及CD1a表达较低的CD4或CD8单阳性细胞。这些淋巴细胞还显示出产生IL-2和IL-4的活性。在新建立的缺乏NK活性的NOD/SCID小鼠的胸腺中也出现了与人类T细胞相似的特征。这些结果表明，在由胸腺上皮细胞组成的小鼠环境中，功能成熟的T细胞可以从人类造血祖细胞在体内发育而来。
