Contribution of B Cells and Antibody to Cardiac Allograft Vasculopathy
Contribution of B Cells and Antibody to Cardiac Allograft Vasculopathy
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DOI：
10.1097/tp.0b013e3181b076cc
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发表时间：
2009-08-27
期刊：
影响因子：
6.2
通讯作者：
Nashan, Bjorn
中科院分区：
文献类型：
--
作者：
Gareau, Alison;Hirsch, Gregory M.;Nashan, Bjorn
背景。本研究的目的是确定同种异体抗体在心脏移植血管病变（AV）发展中的作用。房颤是慢性心脏移植排斥反应导致移植后10年移植物丧失的主要病理指标。在房颤中，新内膜病变形成导致管腔阻塞和移植器官损伤。AV是由t细胞介导的，但B细胞和抗体在AV发展中的作用一直存在争议。没有临床相关免疫抑制剂存在的研究。在我们的研究中，我们使用环孢素A，一种钙调磷酸酶抑制剂。两种b细胞缺乏症模型作为C3H/HeJ腹主动脉移植的受体；8周时采集移植物。T细胞和b细胞免疫缺陷小鼠（RAG1(-/-)）接受被动转移抗c3h抗体，培养136只小鼠。对照组和实验组均每日给予环孢素A。采用α -肌动蛋白染色法鉴定新生内膜中的肌成纤维细胞。b细胞缺陷B6小鼠的病变大小与对照小鼠无显著差异。b细胞缺陷小鼠和野生型小鼠的病变显示出相似水平的α -肌动蛋白阳性。抗体被动转移到RAG1（-/-）小鼠，导致小的α -actin阳性病变。B细胞不需要AV的发展，但同种异体抗体的存在可以促进AV的发展。基于一项体外研究，我们假设同种异体抗体通过启动补体介导的平滑肌细胞杀伤来介导AV。有趣的是，我们发现b细胞缺陷小鼠和接受抗体的小鼠的新内膜病变显示肌成纤维细胞中存在a-actin。
Background. The aim of this study was to determine the role of alloantibody in the development of cardiac allograft vasculopathy (AV). AV is the main pathologic indicator of chronic cardiac graft rejection resulting in graft loss at 10 years posttransplant. In AV, a neointimal lesion forms resulting in luminal occlusion and damage to the transplanted organ. AV is T-cell mediated, but the role played by B cells and antibody in AV development has been controversial. No studies have been conducted in the presence of a clinically relevant immunosuppressant. In our study, we use cyclosporin A, a calcineurin inhibitor.Methods. Two models of B-cell deficiency were used as recipients of a C3H/HeJ abdominal aortic graft; grafts were harvested at 8 weeks. T- and B-cell immunodeficient mice (RAG1(-/-)) received passively transferred anti-C3H antibody, raised in 136 mice. Cyclosporin A was administered daily to both control and experimental groups. alpha-Actin staining was used to identify myofibroblasts in the neointima.Results. Lesions in B-cell-deficient B6 mice were not significantly different in size from those of control mice. Lesions in both B-cell-deficient and wild-type mice showed similar levels of alpha-actin positivity. Passive transfer of antibody to RAG1(-/-) mice resulted in small, alpha-actin-positive lesions.Conclusions. B cells are not required for the development of AV, but the presence of an alloantibody can contribute to AV. We hypothesize that the alloantibody mediates AV by initiating complement-mediated killing of smooth muscle cells, based on an in vitro work. Of interest, we found that the neointimal lesions of B-cell-deficient mice and mice that received antibody showed the presence of a-actin in myofibroblasts.