MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination.
MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination.
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DOI：
10.1002/stem.1234
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发表时间：
2012-11
期刊：
影响因子：
5.2
通讯作者：
Lane, Thomas E.
中科院分区：
文献类型：
--
作者：
Weinger, Jason G.;Weist, Brian M.;Plaisted, Warren C.;Klaus, Suzi M.;Walsh, Craig M.;Lane, Thomas E.
将同系神经祖细胞（NPC）移植到持续感染小鼠肝炎病毒（JHMV）的JHM株的小鼠中，导致向少突胶质细胞祖细胞（OPC）的分化增强，这与髓鞘再生、轴突保留和临床改善有关。在神经炎性脱髓鞘条件下，同种异体NPC是否耐受或诱导免疫介导的排斥反应是有争议的，并且定义不清。我们已经使用了JHMV诱导的脱髓鞘模型，以评估移植同种异体NPC在中枢神经系统（CNS）与建立免疫介导的脱髓鞘小鼠的抗原性。培养的NPC组成性表达共刺激分子CD 80/CD 86，IFN-γ处理诱导MHC I类和II类抗原的表达。注射同种异体C57 BL/6 NPC（H-2b背景）导致Balb/c（H-2d背景）中的迟发型超敏反应（DTH）应答，其与同种异体NPC共培养后的T细胞增殖和IFN-γ分泌相关。将MHC不匹配的NPC移植到JHMV感染的小鼠中导致编码T细胞趋化因子CXCL 9和CXCL 10的转录物增加，这与NPC排斥相关的T细胞浸润增加相关。用T细胞亚群特异性耗竭抗体治疗MHC错配小鼠可增加同种异体NPC的存活率，而不影响向少突胶质细胞谱系的定型。总的来说，这些结果表明，同种异体NPC是抗原性的，T细胞有助于移植到发炎的CNS后的排斥反应，这表明免疫调节治疗可能是必要的，以延长同种异体细胞的存活。
Transplantation of syngeneic neural progenitor cells (NPCs) into mice persistently infected with the JHM strain of mouse hepatitis virus (JHMV) results in enhanced differentiation into oligodendrocyte progenitor cells (OPCs) that is associated with remyelination, axonal sparing, and clinical improvement. Whether allogeneic NPCs are tolerated or induce immune-mediated rejection is controversial and poorly defined under neuroinflammatory demyelinating conditions. We have used the JHMV-induced demyelination model to evaluate the antigenicity of transplanted allogeneic NPCs within the central nervous system (CNS) of mice with established immune-mediated demyelination. Cultured NPCs constitutively expressed the co-stimulatory molecules CD80/CD86 and IFN-γ treatment induced expression of MHC class I and II antigens. Injection of allogeneic C57BL/6 NPCs (H-2b background) led to a delayed type hypersensitivity (DTH) response in Balb/c (H-2d background) associated with T cell proliferation and IFN-γ secretion following co-culture with allogeneic NPCs. Transplantation of MHC-mismatched NPCs into JHMV-infected mice resulted in increased transcripts encoding the T cell chemoattractant chemokines CXCL9 and CXCL10 that correlated with increased T cell infiltration that was associated with NPC rejection. Treatment of MHC-mismatched mice with T cell subset-specific depleting antibodies increased survival of allogeneic NPCs without affecting commitment to an oligodendroyte lineage. Collectively, these results show that allogeneic NPCs are antigenic and T cells contribute to rejection following transplantation into an inflamed CNS suggesting that immunomodulatory treatments may be necessary to prolong survival of allogeneic cells.
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影响因子：
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