Allorecognition of human neural stem cells by peripheral blood lymphocytes despite low expression of MHC molecules:: role of TGF-β in modulating proliferation
Allorecognition of human neural stem cells by peripheral blood lymphocytes despite low expression of MHC molecules:: role of TGF-β in modulating proliferation
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DOI：
10.1093/intimm/dxm079
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Baggi, Fulvio
中科院分区：
文献类型：
--
作者：
Ubiali, Federica;Nava, Sara;Baggi, Fulvio
已经提出神经干细胞（NSC）移植作为恢复受损脑组织的手段，由于I类和II类MHC以及共刺激分子的低表达，在各种实验模型中低NSC免疫原性的报道更有可能提供这种可能性。我们研究了在正常培养条件下生长的人NSC系的免疫原性，并在促炎细胞因子IFN-γ和肿瘤坏死因子α的存在下，通过单向混合淋巴细胞反应（MLR）实验与来自8个HLA不相容供体的外周血淋巴细胞。神经干细胞刺激淋巴细胞增殖在几乎所有的捐助者测试，与刺激指数的范围内的低端分布曲线的MLR捐助者之间。MLR结果阴性的健康受试者是NSC单倍型的最佳相容供体。由于我们观察到低的MLR反应，我们研究了神经干细胞是否可能发挥任何免疫调节活性。我们检测到转录和释放的免疫调节分子转化生长因子β（TGF-β）-1;此外，在MLR实验中加入TGF-β 1下调增殖反应。为了进一步证实人类神经干细胞的免疫潜力，我们研究了来自C57 BL/6小鼠的免疫活性细胞对神经干细胞的异种识别，表明神经干细胞可以在体外引发同种（异种）反应。我们的数据表明，神经干细胞具有低但不可忽略的免疫原性潜力，足以激活外周淋巴细胞。TGF-β 1的分泌可能与神经干细胞的免疫原性相平衡。然而，异基因神经干细胞移植可能会在长期诱导免疫激活，从而失去其治疗效果的可能性，不应被忽视，值得进一步研究。
Neural stem cells (NSCs) transplantation has been proposed as a means of restoring damaged brain tissue, a possibility rendered more likely by reports of low NSCs immunogenicity in various experimental models because of low expression of MHC class I and II as well as co- stimulatory molecules. We investigated the immunogenicity of a human NSC line grown in normal culture conditions and in the presence of pro- inflammatory cytokines IFN-gamma and tumor necrosis factor alpha by one-way mixed lymphocyte reaction (MLR) experiments with peripheral blood lymphocytes from eight HLA-incompatible donors. NSCs stimulated lymphocyte proliferation in almost all donors tested, with stimulation indices in the range of the low-end distribution curve of MLR between donors. The healthy subject that gave negative MLR results was the best compatible donor with respect to NSC haplotype. Since we observed low MLR responses overall, we studied if NSCs might exert any immunomodulatory activity. We detected transcription and release of the immunomodulatory molecule transforming growth factor beta (TGF-beta)-1; moreover, the addition of TGF-beta 1 in MLR experiments down-regulated proliferative responses. To further confirm the immunological potential of human NSCs, we studied xenogeneic recognition of NSCs by immunocompetent cells derived from C57BL/6 mice, showing that NSCs can elicit an allo(xeno) response ex vivo. Our data indicate that NSCs have low but not negligible immunogenic potential that is sufficient to activate peripheral lymphocytes. Secretion of TGF-b1 might balance the immunogenicity of NSCs. Nevertheless, the possibility that allo-NSCs grafting might induce in the long term an immune activation, thus vanishing their therapeutical effect, should not be overlooked and deserves further investigation.