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
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DOI：
10.1172/jci12080
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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衰竭（ARF）的发病机制有关，但涉及的单个细胞类型的作用在很大程度上是未知的。最近的间接证据表明，T细胞可能在ARF小鼠模型中发挥重要作用。在目前的研究中，我们发现T细胞缺陷的小鼠（nu/nu小鼠）在功能上和结构上都受到保护，免受缺血后肾损伤。用野生型T细胞重建nu/nu小鼠可恢复缺血后损伤。然后，我们分析了单个T细胞亚群对缺血后损伤的作用，发现CD 4（+）T细胞缺乏的小鼠，而不是CD 8（+）T细胞缺乏的小鼠，明显免受ARF的影响。当用野生型CD 4（+）T细胞重建CD 4缺陷小鼠恢复缺血后损伤时，获得了CD 4（+）T细胞病理生理作用的直接证据。此外，缺乏共刺激分子CD 28或产生IFN-γ能力的CD 4（+）T细胞的过继转移不足以恢复损伤表型。这些结果表明，CD 4（+）T细胞是缺血性ARF的重要介质，靶向该细胞可能产生新的治疗方法。
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.