Neural progenitor cells lack immunogenicity and resist destruction as allografts
Neural progenitor cells lack immunogenicity and resist destruction as allografts
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DOI：
10.1634/stemcells.21-4-405
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发表时间：
2003-01-01
期刊：
影响因子：
5.2
通讯作者：
Young, MJ
中科院分区：
文献类型：
--
作者：
Hori, J;Ng, TF;Young, MJ
从哺乳动物中枢神经系统（CNS）中分离的多能、自我更新的干细胞和祖细胞已被证明可以作为同种异体移植物移植到神经轴的各个部位后存活。然而，这种类型的研究很少揭示细胞本身的免疫特性，主要是因为很少了解细胞移植到免疫特权部位时的内在免疫原性特性。因此，我们通过将CNS祖细胞移植到常规（即非免疫特权）部位，即肾包膜下方，研究了CNS祖细胞的免疫原性和抗原特性。我们的研究结果表明，同种异体中枢神经系统祖细胞在常规部位存活至少4周，在此期间，它们既不会使宿主敏感，也不会表达可检测水平的主要组织相容性复合体（MHC） I类或II类。这些体内数据与流式细胞术结果一致，显示CNS祖细胞在基线或在10%的血清中分化时不表达MHC I类或II类。然而，暴露于干扰素γ可可逆地上调这些关键移植抗原的表达。综上所述，这些结果表明中枢神经系统祖细胞具有固有的免疫特权。由于中枢神经系统祖细胞同种异体移植物在宿主特异性致敏后在肾包膜下被排斥，中枢神经系统祖细胞能够显示同种异体抗原，尽管不是免疫原性的形式。
Multipotent, self-renewing stem and progenitor cells isolated from the mammalian central nervous system (CNS) have been shown to survive as allografts following transplantation to sites throughout the neuraxis. However, studies of this type shed little light upon the immunologic properties of the cells themselves, primarily because little is learned about the intrinsic immunogenic properties of a cell when it is grafted into an immune-privileged site. We have therefore investigated the immunogenic and antigenic properties of CNS progenitor cells by grafting them into a conventional (i.e., non-immune-privileged) site, namely, beneath the kidney capsule. Our results indicate that allogeneic CNS progenitor cells survive at least 4 weeks in a conventional site, during which time they neither sensitize their hosts nor express detectable levels of major histocompatibility complex (MHC) class I or II. These in vivo data are in accord with flow cytometric results showing that CNS progenitor cells do not express MHC class I or class II, either at baseline or upon differentiation in 10% serum. Exposure to interferon gamma, however, reversibly upregulates expression of these key transplantation antigens. Together, these results reveal CNS progenitor cells to possess inherent immune privilege. Since CNS progenitor cell allografts were rejected beneath the kidney capsule following specific sensitization of the host, CNS progenitor cells were able to display alloantigens, albeit not in an immunogenic form.