Lai L-W, Yong K-C, Igarashi S, Lien Y-Hh
Department of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
Kidney Int. 2007 Jun;71(12):1223-31. doi: 10.1038/sj.ki.5002203. Epub 2007 Mar 21.
T cells are thought to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI); however, earlier studies have not found significant T-cell numbers in the kidney following injury. In this study we test the hypothesis that T cells transiently infiltrate the kidney following reperfusion and leave behind T-cell-derived cytokines such as interferons and interleukins, thus triggering an inflammatory reaction. An early rise of infiltrating T cells was coupled with a decrease in both circulating lymphocytes and CD4+ cells of periarterial lymphocyte aggregates. The renal expression of several chemokines was rapidly and markedly increased by ischemia-reperfusion (IR). Sphingosine-1-phosphate type 1 receptor agonists have been shown to protect kidneys from injury. One of these agonists given before IR significantly reduced histologically assessed renal injury, circulating lymphocyte numbers, and renal T-cell infiltration. This pretreatment did not, however, affect the increase in T-cell chemokines but caused an increase in CD4+ cells in the renal lymphatic system. We conclude that T-cell infiltration is an early event after IRI and is mediated by several chemokines. Sphingosine-1-phosphate receptor agonists reduce renal injury and T-cell infiltration in spite of chemokine generation by inhibiting T-cell mobilization from both renal and extra-renal lymphoid tissue.
T细胞被认为参与了肾缺血再灌注损伤(IRI)的发病机制;然而,早期研究并未发现损伤后肾脏中有大量T细胞。在本研究中,我们检验了这样一个假设:再灌注后T细胞会短暂浸润肾脏,并留下T细胞衍生的细胞因子,如干扰素和白细胞介素,从而引发炎症反应。浸润性T细胞的早期增加与循环淋巴细胞和动脉周围淋巴细胞聚集处的CD4+细胞数量减少相关。缺血再灌注(IR)迅速且显著地增加了几种趋化因子在肾脏中的表达。1-磷酸鞘氨醇1型受体激动剂已被证明可保护肾脏免受损伤。在IR之前给予其中一种激动剂可显著减轻组织学评估的肾损伤、循环淋巴细胞数量和肾脏T细胞浸润。然而,这种预处理并未影响T细胞趋化因子的增加,而是导致肾淋巴系统中CD4+细胞增加。我们得出结论,T细胞浸润是IRI后的早期事件,由几种趋化因子介导。1-磷酸鞘氨醇受体激动剂尽管会产生趋化因子,但通过抑制T细胞从肾内和肾外淋巴组织的动员,减轻了肾损伤和T细胞浸润。