人类胚胎干细胞及其衍生的神经干细胞的免疫原性  

The study on the immunogenicity of hESCs and the derived NSCs

作　　者：黎逢光[1] 李朝武[2] 唐洲平[1] 柴竞艳[1] 湛彦强[1] 张苏明[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]解放军第一六一医院神经内科

出　　处：《中华神经科杂志》2007年第12期832-836,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金(30370505);国家自然科学基金青年基金(30600188)

摘　　要：目的体外观察人类胚胎干细胞(hESCs)及其衍生的神经干细胞(NSCs)的免疫原性。方法运用流式细胞仪检测 hESCs 及其衍生的 NSCs 表面 HLA-Ⅰ类分子(HLA-ABC)、HLA-Ⅱ类分子(HLA-DR、-DP、-DQ)的组成型表达,并观察在30 ng/ml 重组人干扰素-γ(IFN-γ)诱导作用下 NSCs细胞表面 HLA-Ⅰ、HLA-Ⅱ诱导型表达的情况。同时通过将 IFN-γ诱导前后的 NSCs 与健康人外周血淋巴细胞共培养,观察淋巴细胞增殖的程度,了解其免疫反应情况。结果在未分化前 hESCs 表面仅少量表达 HLA-Ⅰ类抗原(6.18%),几乎没有 HLA-Ⅱ类抗原的表达;经诱导分化成 NSCs 后 HLA-Ⅰ类抗原表达有所增加(23.56%),HLA-Ⅱ类抗原表达亦轻度增高(1.28%、1.73%);经 IFN-γ诱导后,NSCs 表面 HLA-Ⅰ类抗原表达(46.43%)明显上调,HLA-Ⅱ类抗原的表达(8.73%、10.57%)也进一步地上调,且其刺激淋巴细胞发生增殖反应的能力也进一步增强。结论 hESCs 衍生的 NSCs 具有一定的免疫原性,可能会诱导针对 HLA-Ⅰ类分子的排斥反应,而在宿主的机体处于某些炎症或应激状态及移植局部存在炎症反应时,有可能进一步诱导针对 HLA-Ⅱ类分子的免疫反应。Objective To study the immunogenicity of human embryonic stem cells （hESCs） and the derived neural stem cells （NSCs） in vitro. Methods The constitutive expression of human leucocyte antigen （HLA） I and lI in hESCs and the NSCs derived from these hESCs were detected by flow cytometry （FCM）, as well as the expression of HLA- I , II in NSCs induced by 30 ng/ml recombination human interferon-γ （IFN-γ）. Meanwhile, the NSCs before and after induction of IFN-γ, were co-cultured with peripheral blood lymphocyte obtained from healthy person. Lymphocyte proliferation standing for the immunoreactivity of NSCs was then investigated. Results The hESCs slightly expressed HLA- I （6. 18% ） and hardly any HLA- II before differentiation. However, the NSCs expressed more HLA- I （ 23.56% ） as well as HLA- II （ 1.28 %, 1.73 % ） than the hESCs did. Both HLA- I （ 46.43 % ） and HLA- II （ 8.73 %, 10. 57% ） expressed by the NSCs after they were induced by IFN-γ were up-regulated. Conclusions hESCs express certain level of HLA- I molecules but do not constitutively express HLA- II molecules. The derived NSCs express heavy HLA- I and a little HLA-II , when treated by IFN-γ they can inducibly up- regulated both molecules. The NSCs derived from HESCs are of immunogenicity, which induce rejection aiming at HLA- I molecules or even at HLA-II molecules when the host is inflammative or under stress, which can result in a failure of cellular transplantation.

关 键 词：干细胞 细胞分化 组织相容性抗原 干细胞移植 

分 类 号：R392.1[医药卫生—免疫学]