期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 12, 期 2, 页码 313-321出版社
WILEY
DOI: 10.1111/j.1600-6143.2011.03836.x
关键词
Antibody-mediated rejection; chronic allograft vasculopathy; Fc receptors; heart transplantation; NK cells
资金
- Roche Organ Transplant Research Foundation
- NIH [RO1 HL071932]
- American Society of Transplantation
Chronic allograft vasculopathy (CAV) in murine heart allografts can be elicited by adoptive transfer of donor specific antibody (DSA) to class I MHC antigens and is independent of complement. Here we address the mechanism by which DSA causes CAV. B6.RAG1-/- or B6.RAG1-/-C3-/- (H-2b) mice received B10.BR (H-2k) heart allografts and repeated doses of IgG2a, IgG1 or F(ab)2 fragments of IgG2a DSA (anti-H-2k). Intact DSA regularly elicited markedly stenotic CAV in recipients over 28 days. In contrast, depletion of NK cells with anti-NK1.1 reduced significantly DSA-induced CAV, as judged morphometrically. Recipients genetically deficient in mature NK cells (?-chain knock out) also showed decreased severity of DSA-induced CAV. Direct NK reactivity to the graft was not necessary. F(ab)2 DSA fragments, even at doses twofold higher than intact DSA, were inactive. Graft microvascular endothelial cells responded to DSA in vivo by increased expression of phospho-extracellular signal-regulated kinase (pERK), a response not elicited by F(ab)2 DSA. We conclude that antibody mediates CAV through NK cells, by an Fc dependent manner. This new pathway adds to the possible mechanisms of chronic rejection and may relate to the recently described C4d-negative chronic antibody-mediated rejection in humans.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据