Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.
Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.
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DOI：
10.1002/stem.1760
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发表时间：
2014-10
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.;Plaisted, Warren C.;Maciejewski, Sonia M.;Lanier, Lewis L.;Walsh, Craig M.;Lane, Thomas E.
关键词：
将主要组织相容性复合体（MHC）错配的小鼠神经前体细胞（NPC）移植到持续感染嗜神经性小鼠肝炎病毒（JHMV）JHM株的小鼠中，导致部分由T细胞介导的快速排斥反应。然而，在病毒诱导的神经系统疾病模型中，先天免疫应答对同种异体移植排斥反应的贡献还没有得到很好的定义。在此，我们证明，自然杀伤（NK）细胞表达活化受体NKG 2D参与移植异基因NPC排斥反应在小鼠持续感染JHMV。来自C57 BL/6（H-2b）小鼠的培养NPC表达NKG 2D配体视黄酸早期前体转录物（RAE）-1，但在分化为神经胶质或神经元后表达显著降低。RAE-1+ NPC对NK细胞介导的杀伤敏感，而RAE-1-细胞对裂解有抗性。将C57 BL/6衍生的NPC移植到JHMV感染的BALB/c（H-2d）小鼠中导致NKG 2D + CD 49 b + NK细胞浸润，并且用NKG 2D特异性阻断抗体处理增加了同种异体NPC的存活。此外，将分化的RAE-1同种异体NPC移植到JHMV感染的BALB/c小鼠中导致存活率提高，突出了NKG 2D：RAE-1信号传导轴在同种异体移植排斥中的作用。我们还表明，同种异体NPC移植到JHMV感染的小鼠导致感染的移植细胞，这表明这些细胞可能是感染的目标。培养细胞的病毒感染增加RAE-1表达，导致通过NKG 2D识别增强NK细胞介导的杀伤。总的来说，这些结果表明，在病毒诱导的脱髓鞘模型中，NK细胞通过NKG 2D信号传导途径促进同种异体NPC的排斥。
Transplantation of major histocompatibility complex (MHC)-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2b) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1+ NPCs were susceptible to NK cell-mediated killing whereas RAE-1- cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2d) mice resulted in infiltration of NKG2D+CD49b+ NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Further, transplantation of differentiated RAE-1- allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D:RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway.
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DOI：
10.1196/annals.1444.014
发表时间：
2008-01-01
期刊：
YEAR IN NEUROLOGY 2008
影响因子：
--
作者：
Ben-Hur, Tamir;Goldman, Steven A.
通讯作者：
Goldman, Steven A.
影响因子：
6
作者：
Brück, W
通讯作者：
Brück, W
影响因子：
14.5
作者：
De Stefano, N;Matthews, PM;Arnold, DL
通讯作者：
Arnold, DL
影响因子：
3.7
作者：
CASTRO, RF;EVANS, GD;PERLMAN, S
通讯作者：
PERLMAN, S
影响因子：
6
作者：
Feuer, R;Mena, I;Whitton, JL
通讯作者：
Whitton, JL