Th1 adaptive immune responses in cardiac graft arteriosclerosis: deleterious or beneficial?
Th1 adaptive immune responses in cardiac graft arteriosclerosis: deleterious or beneficial?
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心脏移植物动脉硬化中的 Th1 适应性免疫反应：有害还是有益？
DOI：
10.1161/circulationaha.106.651521
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发表时间：
2006
期刊：
影响因子：
37.8
通讯作者：
Tellides,George
中科院分区：
文献类型：
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作者：
Tellides,George
在缺乏适应性免疫反应的情况下，心脏移植不会被排斥，例如，在遗传相同的供体和宿主之间或向患有严重联合免疫缺陷的受体进行移植时。对同种异体移植物的适应性免疫的激活会引起针对供体实质或血管细胞的破坏性反应，称为急性排斥。在存在足够的免疫抑制的情况下，急性排斥反应被抑制；然而，可能会发生慢性排斥反应，表现为内膜扩张和血管尺寸重塑导致的导管动脉管腔损失，称为移植物动脉硬化。 1 病理结果和对免疫抑制剂敏感性的差异表明，与急性移植物排斥相比，慢性移植物衰竭是由不同同种异体移植物隔室中的不同机制引起的。移植物动脉硬化的确切发病机制尚不清楚，尽管人们普遍认为移植物动脉硬化至少部分是同种免疫过程，因为动脉硬化变化仅限于同种异体移植物的血管床而不受宿主脉管系统的影响。适应性免疫可能激活多种效应机制，导致小鼠移植模型中的慢性移植排斥。 1 虽然它不是导致移植物动脉硬化的唯一因素，但 Th1 细胞因子干扰素 (IFN)- 的证据尤其令人信服。在小鼠移植模型中，血清学中和或遗传性干扰素的缺失会减少移植动脉的内膜扩张。 2, 3 此外，在嵌合人-小鼠模型中，抗体中和 IFN 可预防同种异体 T 细胞介导的内皮功能障碍、内膜增厚和向外血管重塑；给予干扰素会加速这些效应；而外源性IFN-α在白细胞缺失的情况下就足以引起动脉硬化的变化。 4-6 然而，尚缺乏 IFN-在临床心脏移植中的致病作用的明确证据。
Heart transplants are not rejected in the absence of adaptive immune responses, eg, in transplantations between genetically identical donors and hosts or to recipients with severe combined immunodeficiencies. Activation of adaptive immunity to an allograft causes destructive responses against donor parenchymal or vascular cells, called acute rejection. In the presence of adequate immunosuppression, acute rejection is suppressed; however, chronic rejection may occur, manifesting as conduit arterial lumen loss resulting from expansion of the tunica intima and remodeling of vessel size, called graft arteriosclerosis. 1 The differences in pathological findings and in sensitivity to immunosuppressive agents suggest that chronic graft failure arises from different mechanisms operative in separate allograft compartments than in acute graft rejection. The precise pathogenesis of graft arteriosclerosis is unknown, although there is broad consensus that it is, at least in part, an alloimmune process in that the arteriosclerotic changes are limited to the vascular bed of the allograft and spare the host vasculature. Adaptive immunity may activate a variety of effector mechanisms that cause chronic graft rejection in murine transplantation models. 1 Although it is not the only factor that can cause graft arteriosclerosis, the evidence for the signature Th1 cytokine, interferon (IFN)-, is particularly compelling. In mouse transplantation models, serological neutralization or the genetic absence of IFN-reduces intimal expansion of graft arteries. 2, 3 Moreover, in a chimeric human-mouse model, antibody neutralization of IFN-prevents allogeneic T cell–mediated endothelial dysfunction, intimal thickening, and outward vascular remodeling; administration of IFN-accelerates these effects; and exogenous IFN-in the absence of leukocytes is sufficient to cause the arteriosclerotic changes. 4–6 However, definitive evidence for a pathogenetic role of IFN-in clinical cardiac transplantation is lacking.