Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure
Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure
复制标题
DOI：
10.1172/jci200112080
复制
发表时间：
2001-11-01
影响因子：
15.9
通讯作者：
Rabb, H
中科院分区：
文献类型：
--
作者：
Burne, MJ;Daniels, F;Rabb, H
白细胞与缺血性急性肾功能衰竭(ARF)的发病机制有关，但所涉及的单个细胞类型的作用在很大程度上尚不清楚。最近的间接证据表明，T细胞可能在ARF的小鼠模型中发挥重要作用。在目前的研究中，我们发现T细胞缺陷小鼠(nu/nu小鼠)在功能和结构上都受到保护，免受缺血后肾损伤。野生型T细胞重建nu/nu小鼠修复了缺血后的损伤。然后，我们分析了单个T细胞亚群对缺血后损伤的贡献，发现CD4(+)T细胞缺陷的小鼠，但CD8(+)T细胞缺陷的小鼠，显著免受ARF的保护。当用野生型CD4(+)T细胞重建的CD4缺陷小鼠恢复缺血后的损伤时，获得了CD4(+)T细胞的病理生理作用的直接证据。此外，过继转移缺乏共刺激分子CD28或产生干扰素-γ能力的CD4(+)T细胞不足以恢复损伤表型。这些结果表明，CD4(+)T细胞是缺血性ARF的重要介质，靶向这一细胞可能会产生新的治疗方法。
Leukocytes have been implicated in the pathogenesis of ischemic acute renal failure (ARF), but the roles of the individual cell types involved are largely unknown. Recent indirect evidence suggests that T cells may play an important role in a murine model of ARF. In the current study, we found that mice deficient in T cells (nu/nu mice) are both functionally and structurally protected from postischemic renal injury. Reconstitution of nu/nu mice with wild-type T cells restored postischemic injury. We then analyzed the contribution of the individual T cell subsets to postischemic injury and found that mice deficient in CD4(+) T cells, but not mice deficient in CD8(+) T cells, were significantly protected from ARF. Direct evidence for a pathophysiologic role of the CD4(+) T cell was obtained when reconstitution of CD4-deficient mice with wild-type CD4(+) T cells restored postischemic injury. In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype. These results demonstrate that the CD4(+) T cell is an important mediator of ischemic ARF, and targeting this cell may yield novel therapies.