Pathophysiological role of T lymphocytes in renal ischemia-reperfusion injury in mice

作者：Hamid Rabb, Frank Daniels, Michael A. O’Donnell, Mahmud Haq, Sabiha R. Saba, William F. Keane, Winson W. Tang · 发表于：American Journal of Physiology-Renal Physiology · 年份：2000 · DOI：10.1152/ajprenal.2000.279.3.f525 · 被引用次数：354 · 研究领域：Acute Kidney Injury Research、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Renal Transplantation Outcomes and Treatments

Mononuclear cell infiltrates are found in human renal ischemia-reperfusion injury (IRI), and peritubular T lymphocytes have been identified in experimental IRI. However, the role of T cells in the pathogenesis of renal IRI is unknown. We hypothesized that T cells are one of the important mediators of renal IRI. To test this hypothesis, we used an established mouse model of renal IRI, and evaluated mice with genetically engineered deficiency of both CD4+ and CD8+ T cells. At 48 h postischemia, CD4/CD8-knockout (KO) mice had marked improvement in renal function compared with control C57BL/6 mice (serum creatinine: 0.7 +/- 0.4 vs. 2.5 +/- 0.3 mg/dl, respectively; P < 0.05). Neutrophil infiltration into postischemic kidney was reduced in CD4/CD8 KO mice, compared with control mice, at both 24 h [polymorphonuclear neutrophils (PMNs)/10 high power fields: 714 +/- 354 vs. 3,514 +/- 660, respectively; P < 0.05] and 48 h (88 +/- 32 vs. 1,979 +/- 209, respectively; P < 0.05). Tubular necrosis score in CD4/CD8 KO mice, compared with control mice, was significantly less at 48 h (0.4 +/- 0.1 vs. 2.4 +/- 0.2, respectively; P < 0.05). Because adhesion between T cells and renal tubular epithelial cells (RTECs) may underlie the pathophysiological role of T cells in renal IRI, we also measured T cell adhesion to primary murine RTECs in vitro. Exposure of RTECs to 2 h of hypoxia followed by 1 h of reoxygenation increased T cell adhesion more than twofold. Phorbol ester treatment, which activate...