Li Li, Huang Liping, Sung Sun-sang J, Lobo Peter I, Brown Michael G, Gregg Randal K, Engelhard Victor H, Okusa Mark D
Department of Medicine, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
J Immunol. 2007 May 1;178(9):5899-911. doi: 10.4049/jimmunol.178.9.5899.
Previous work has shown that ischemia-reperfusion (IR) injury (IRI) is dependent on CD4(+) T cells from naive mice acting within 24 h. We hypothesize that NKT cells are key participants in the early innate response in IRI. Kidneys from C57BL/6 mice were subjected to IRI (0.5, 1, 3, and 24 h of reperfusion). After 30 min of reperfusion, we observed a significant increase in CD4(+) cells (145% of control) from single-cell kidney suspensions as measured by flow cytometry. A significant fraction of CD4(+) T cells expressed the activation marker, CD69(+), and adhesion molecule, LFA-1(high). Three hours after reperfusion, kidney IFN-gamma-producing cells were comprised largely of GR-1(+)CD11b(+) neutrophils, but also contained CD1d-restricted NKT cells. Kidney IRI in mice administered Abs to block CD1d, or deplete NKT cells or in mice deficient of NKT cells (Jalpha18(-/-)), was markedly attenuated. These effects were associated with a significant decrease in renal infiltration and, in activation of NKT cells, and a decrease in IFN-gamma-producing neutrophils. The results support the essential role of NKT cells and neutrophils in the innate immune response of renal IRI by mediating neutrophil infiltration and production of IFN-gamma.
先前的研究表明，缺血再灌注（IR）损伤（IRI）依赖于来自未接触过抗原的小鼠的CD4(+) T细胞在24小时内发挥作用。我们假设自然杀伤T（NKT）细胞是IRI早期固有免疫反应的关键参与者。对C57BL/6小鼠的肾脏进行IRI处理（再灌注0.5、1、3和24小时）。再灌注30分钟后，通过流式细胞术检测发现，单细胞肾脏悬液中的CD4(+)细胞显著增加（为对照组的145%）。相当一部分CD4(+) T细胞表达活化标志物CD69(+)和黏附分子LFA-1(高表达)。再灌注3小时后，肾脏中产生干扰素-γ的细胞主要由GR-1(+)CD11b(+)中性粒细胞组成，但也包含CD1d限制性NKT细胞。给小鼠注射抗体以阻断CD1d、清除NKT细胞或使用NKT细胞缺陷小鼠（Jalpha18(-/-)），肾脏IRI均明显减轻。这些效应与肾脏浸润显著减少、NKT细胞活化以及产生干扰素-γ的中性粒细胞减少有关。结果支持NKT细胞和中性粒细胞通过介导中性粒细胞浸润和干扰素-γ产生在肾脏IRI固有免疫反应中发挥重要作用。
