The natural killer cell activating receptor, NKG2D, is critical to antibody-dependent chronic rejection in heart transplantation.
The natural killer cell activating receptor, NKG2D, is critical to antibody-dependent chronic rejection in heart transplantation.
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天然杀伤细胞激活受体NKG2D对抗体依赖性慢性抑制至关重要。
DOI：
10.1111/ajt.16690
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发表时间：
2021-11
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影响因子：
--
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慢性排斥反应是实体器官移植中最紧迫的临床挑战之一。有趣的是，在异位心脏移植小鼠模型中，抗体依赖、nk细胞介导的慢性同种异体心脏移植血管病变发生在一些供体-受体株组合中，而不是其他。在这项研究中，我们试图确定这种无法解释的现象背后的机制。来自MHC不匹配供体的同种异体心脏移植物被移植到免疫缺陷的C57Bl/6中。rag−/−受体，然后给予针对供体MHC I类抗原的单克隆抗体。我们发现来自C3H供体的心脏有明显的同种异体血管病变，但BALB/c同种异体移植物几乎完全保护不受损伤。我们发现受体NK细胞表型或对激活信号的内在反应在C3H和BALB/c同种异体移植物受体之间没有差异。然而，来自C3H异体移植的心脏内皮细胞显示出大约两倍的高表达Rae-1，一种NK细胞受体NKG2D的激活配体。重要的是，抗NKG2D的中和抗体消除了C3H异体移植物受体发生的异体血管病变，即使存在供体特异性抗体。因此，激活NK细胞受体NKG2D在慢性同种异体心脏移植血管病变模型中是必要的，NK激活配体的株依赖性表达与该疾病的发展相关。
Chronic rejection is amongst the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, NK-cell mediated chronic cardiac allograft vasculopathy occurs in some donor-recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from MHC mismatched donors were transplanted into immune-deficient C57Bl/6.rag−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately two-fold higher expression of Rae-1, an activating ligand of the NK cell receptor NKG2D. Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy and strain-dependent expression of NK activating ligands correlates with the development of this disease.
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DOI：
10.1164/rccm.201209-1749oc
发表时间：
2013-06-15
影响因子：
24.7
作者：
Jungraithmayr, Wolfgang;Codarri, Laura;Muenz, Christian
通讯作者：
Muenz, Christian
影响因子：
6.5
作者：
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Mignot, Gregoire
影响因子：
20.3
作者：
Laffont, Sophie;Seillet, Cyril;Guery, Jean-Charles
通讯作者：
Guery, Jean-Charles
影响因子：
32.4
作者：
Hanke, T;Takizawa, H;Raulet, DH
通讯作者：
Raulet, DH
影响因子：
4.4
作者：
Kim, Jim;Chang, Catherine K.;Kang, Sang-Mo
通讯作者：
Kang, Sang-Mo