Acute humoral rejection of renal allografts in CCR5-/- recipients
Acute humoral rejection of renal allografts in CCR5-/- recipients
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DOI：
10.1111/j.1600-6143.2007.02125.x
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发表时间：
2008-03-01
影响因子：
8.8
通讯作者：
Fairchild, R. L.
中科院分区：
文献类型：
--
作者：
Bickerstaffa, A.;Nozaki, T.;Fairchild, R. L.
随着肾移植急性体液性排斥反应（AHR）的日益增多，需要合适的动物模型来研究其潜在机制。缺乏趋化因子受体CCR 5的小鼠受体排斥心脏同种异体移植物，在实质毛细血管中具有显著的C3 d沉积和高血清供体反应性抗体滴度，这些特征与AHR一致。本文观察了B_6. CCR_5（-/-）（H-2（B））受体对A/J（H-2（a））供者MHC不全相合同种异体肾移植的排斥反应。在血肌酐水平正常（28 +/- 7 μ mol/L）的野生型C57 BL/6受体中，A/J肾移植物存活超过100天。所有CCR 5（-/-）受体在移植后21天内（平均13.3 +/- 4天）发生肾移植排斥反应，肌酐升高（90 +/- 31 μ mol/L）。排斥的同种异体移植物有中性粒细胞和巨噬细胞边集，肾小管周围毛细血管弥漫性C3 d沉积，间质出血和水肿，肾小球纤维蛋白沉积。B6.CCR5（-/-）中循环供体反应性抗体滴度比野生型受体高40倍。受体CD 8 T细胞的耗竭并不能避免CCR 5缺陷受体对肾移植物的排斥反应。相反，不能产生抗体的μ MT-/-/CCR 5（-/-）受体不会排斥大多数同种异体肾移植物。总的来说，这些结果表明在CCR 5（-/-）受体中的肾移植物的快速排斥反应，在人肾移植物的AHR期间观察到许多组织病理学特征。
Increasing detection of acute humoral rejection (AHR) of renal allografts has generated the need for appropriate animal models to investigate underlying mechanisms. Murine recipients lacking the chemokine receptor CCR5 reject cardiac allografts with marked C3d deposition in the parenchymal capillaries and high serum donor-reactive antibody titers, features consistent with AHR. The rejection of MHC-mismatched renal allografts from A/J (H-2(a)) donors by B6.CCR5(-/-) (H-2(b)) recipients was investigated. A/J renal allografts survived longer than 100 days in wild-type C57BL/6 recipients with normal blood creatinine levels (28 +/- 7 mu mol/L). All CCR5(-/-) recipients rejected renal allografts within 21 days posttransplant (mean 13.3 +/- 4 days) with elevated creatinine (90 +/- 31 mu mol/L). The rejected allografts had neutrophil and macrophage margination and diffuse C3d deposition in peritubular capillaries, interstitial hemorrhage and edema, and glomerular fibrin deposition. Circulating donor-reactive antibody titers were 40-fold higher in B6.CCR5(-/-) versus wild-type recipients. Depletion of recipient CD8 T cells did not circumvent rejection of the renal allografts by CCR5-deficient recipients. In contrast, mu MT-/-/CCR5(-/-) recipients, incapable of producing antibody, did not reject most renal allografts. Collectively, these results indicate the rapid rejection of renal allografts in CCR5(-/-) recipients with many histopathologic features observed during AHR of human renal allografts.