Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells
Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells
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DOI：
10.1634/stemcells.2005-0188
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发表时间：
2006-02-01
期刊：
影响因子：
5.2
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
--
作者：
Drukker, Micha;Katchman, Helena;Benvenisty, Nissim
来源于人胚胎干细胞（hESC）的分化细胞类型可能在未来用于治疗各种人类疾病。它们成功应用于临床的关键一步是检查移植后可能针对它们发起的免疫反应。我们使用两个实验平台来检查体内白细胞对hESC的应答。首先，使用免疫活性和免疫缺陷小鼠品系来鉴定T细胞作为引起hESC异种排斥的主要成分。第二，将携带来自人来源的外周血白细胞的小鼠用于测试人类白细胞对未分化和分化的hESC的同种异体反应。使用这个模型，我们已经检测到只有一分钟的免疫反应，对未分化以及分化的hESC在1个月的过程中，虽然控制成人移植物反复浸润淋巴细胞和破坏。我们的数据表明，由于低免疫刺激潜力，细胞逃避免疫破坏。然而，一个人的细胞毒性T淋巴细胞克隆，是专门准备识别两个hESC线可以裂解后的细胞主要组织相容性复合物I类（MHC-I）诱导。虽然人胚胎干细胞中的MHC-I水平足以被细胞毒性T细胞排斥，但我们的数据表明细胞的免疫刺激能力非常低。因此，与常规器官移植相比，基于hESC的治疗剂的免疫抑制方案可以大大减少，因为hESC及其衍生物的直接同种异体排斥过程相当弱。
Differentiated cell types derived from human embryonic stem cells (hESCs) may serve in the future to treat various human diseases. A crucial step toward their successful clinical application is to examine the immune response that might be launched against them after transplantation. We used two experimental platforms to examine the in vivo leukocyte response toward hESCs. First, immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that causes xenorejection of hESCs. Second, mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse toward undifferentiated and differentiated hESCs. Using this model, we have detected only a minute immune response toward undifferentiated as well as differentiated hESCs over the course of 1 month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data show that the cells evade immune destruction due to a low immunostimulatory potential. Nevertheless, a human cytotoxic T lymphocyte clone that was specifically prepared to recognize two hESC lines could lyse the cells after major histocompatibility complex class I (MHC-I) induction. Although MHC-I levels in hESCs are sufficient for rejection by cytotoxic T cells, our data suggest that the immunostimulatory capacity of the cells is very low. Thus, immunusuppressive regimens for hESC-based therapeutics could be highly reduced compared with conventional organ transplantation because direct allorejection processes of hESCs and their derivatives are considerably weaker.