Department of Cellular and Molecular Immunology, University of Göttingen, Humboldtallee 34, 37073 Göttingen, Germany.
FASEB J. 2010 Jul;24(7):2164-77. doi: 10.1096/fj.09-134957. Epub 2010 Feb 9.
Multipotent adult germ-line stem cells (maGSCs) and induced pluripotent stem cells (iPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, effects of the immune system on these cells have not been investigated. We have compared the susceptibility of maGSC lines to IL-2-activated natural killer (NK) cells with embryonic stem cell (ESC) lines, iPSCs, and F9 teratocarcinoma cells. The killing of pluripotent cell lines by syngeneic, allogeneic, and xenogeneic killer cells ranged between 48 and 265% in chromium release assays when compared to YAC-1 cells, which served as highly susceptible reference cells. With the exception of 2 maGSC lines, they expressed ligands for the activating NK receptor NKG2D that belong to the RAE-1 family, and killing could be inhibited by soluble NKG2D, demonstrating a functional role of these molecules. Furthermore, ligands of the activating receptor DNAM-1 were frequently expressed. The susceptibility to NK cells might constitute a common feature of pluripotent cells. It could result in rejection after transplantation, as suggested by a reduced teratoma growth after NK cell activation in vivo, but it might also offer a strategy to deplete contaminating pluripotent cells before grafting of differentiated cells.
多能成体生殖细胞系（maGSCs）和诱导多能干细胞（iPSCs）可用于产生用于治疗目的的自体细胞，预计这些细胞将被受者耐受。然而，免疫系统对这些细胞的影响尚未得到研究。我们比较了 maGSC 系对 IL-2 激活的自然杀伤（NK）细胞的敏感性与胚胎干细胞（ESC）系、iPSCs 和 F9 畸胎瘤细胞的敏感性。在铬释放测定中，与用作高度敏感参考细胞的 YAC-1 细胞相比，同种、同种异体和异种杀伤细胞对多能细胞系的杀伤率在 48%至 265%之间。除了 2 个 maGSC 系之外，它们还表达属于 RAE-1 家族的激活 NK 受体 NKG2D 的配体，并且可以通过可溶性 NKG2D 抑制杀伤，表明这些分子具有功能作用。此外，激活受体 DNAM-1 的配体经常表达。对 NK 细胞的敏感性可能是多能细胞的共同特征。这可能导致移植后的排斥，因为体内 NK 细胞激活后畸胎瘤生长减少表明了这一点，但它也可能提供一种在移植分化细胞之前清除污染的多能细胞的策略。
