The classical complement pathway in transplantation: Unanticipated protective effects of C1q and role in inductive antibody therapy
The classical complement pathway in transplantation: Unanticipated protective effects of C1q and role in inductive antibody therapy
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DOI：
10.1111/j.1600-6143.2008.02295.x
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发表时间：
2008-08-01
影响因子：
8.8
通讯作者：
Bishop, D. K.
中科院分区：
文献类型：
--
作者：
Csencsits, K.;Burrell, B. E.;Bishop, D. K.
虽然补体（C）在移植物中的沉积与同种异体移植物排斥反应有关，但所采用的途径尚未建立。此外，有证据表明，C介导的细胞溶解可能是mAb疗法的耐受诱导活性所必需的。因此，我们评估了经典C通路在急性同种异体移植排斥反应中的作用及其对实验性mAb治疗的需求。C1 q缺陷型（C1 q-/-）受体排斥同种异体移植物的速度比野生型（WT）受体快。这种排斥反应与C1 q-/-受体的移植病理恶化有关，但与增强的T细胞反应无关。然而，在C1 q-/-小鼠中，对供体同种抗原的体液反应加速，因为观察到早期IgG反应和移植物内的IgG沉积。此外，在从C1 q-/-受体分离的移植物中观察到C3 d沉积，而不是C4d。为了评估经典C通路在诱导mAb治疗中的作用，C1 q-/-受体接受抗CD 4或抗CD 40 L mAb治疗。C1 q-/-受体中抗CD 4 mAb的保护作用降低，但这种作用与CD 4+细胞的无效耗竭无关。相反，抗CD 40 L mAb的保护作用在C1 q-/-受体中受到较少损害。因此，这项研究揭示了C1 q在排斥过程中的意想不到的作用。
Though complement (C) deposition within the transplant is associated with allograft rejection, the pathways employed have not been established. In addition, evidence suggests that C-mediated cytolysis may be necessary for the tolerance-inducing activities of mAb therapies. Hence, we assessed the role of the classical C pathway in acute allograft rejection and its requirement for experimental mAb therapies. C1q-deficient (C1q-/-) recipients rejected allografts at a faster rate than wild-type (WT) recipients. This rejection was associated with exacerbated graft pathology but not with enhanced T-cell responses in C1q-/- recipients. However, the humoral response to donor alloantigens was accelerated in C1q-/- mice, as an early IgG response and IgG deposition within the graft were observed. Furthermore, deposition of C3d, but not C4d was observed in grafts isolated from C1q-/- recipients. To assess the role of the classical C pathway in inductive mAb therapies, C1q-/- recipients were treated with anti-CD4 or anti-CD40L mAb. The protective effects of anti-CD4 mAb were reduced in C1q-/- recipients, however, this effect did not correlate with ineffective depletion of CD4+ cells. In contrast, the protective effects of anti-CD40L mAb were less compromised in C1q-/- recipients. Hence, this study reveals unanticipated roles for C1q in the rejection process.