Division of Nephrology and Hypertension, Department of Medicine, Hannover Medical School, Hannover, Germany.
Nephrol Dial Transplant. 2014 May;29(5):1020-8. doi: 10.1093/ndt/gft495. Epub 2013 Dec 18.
Altered immune function in patients with renal failure results in both susceptibility to infection and increased inflammatory response. Invariant natural killer T (iNKT) cells are a conserved, immunoregulatory T lymphocyte subset that responds to lipid antigens with near-immediate cytokine production and cytotoxicity. iNKT cells are required for the antibacterial host response. Whether renal failure and renal replacement therapy alter iNKT cell abundance or phenotype has not been investigated.
iNKT cells were studied by flow cytometry in the peripheral blood of patients with acute renal failure, chronic haemo- and peritoneal dialysis (PD), chronic kidney disease and after renal transplantation.
A very marked reduction in iNKT lymphocytes was found in acute renal failure before the first haemodialysis (HD) session. iNKT cells were depleted in end-stage renal disease patients receiving either HD or PD. iNKT cell depletion was accentuated after an HD session. Lesser degrees were observed in patients with non-dialysis-dependent chronic kidney disease. CD56 and CD161 NK cell marker expression was decreased in renal impairment. CD56(+) and CD161(+) iNKT cells produced more interferon-γ than negative cells of the same donor. Within the first year after kidney transplantation, the decrease in iNKT cells and their NK cell markers was reverted.
We describe for the first time that iNKT lymphocytes are reduced in end-stage renal disease and further depleted by HD. iNKT cells are important for early host response including activation of other immune cells and their depletion may contribute to immune dysfunction in renal disease.
肾衰竭患者的免疫功能改变会导致易感染和炎症反应增加。不变自然杀伤 T(iNKT)细胞是一种保守的免疫调节 T 淋巴细胞亚群,对脂质抗原具有近乎即时的细胞因子产生和细胞毒性反应。iNKT 细胞是抗菌宿主反应所必需的。肾衰竭和肾脏替代治疗是否改变 iNKT 细胞的丰度或表型尚未得到研究。
通过流式细胞术研究了急性肾衰竭、慢性血液和腹膜透析(PD)、慢性肾脏病和肾移植后的患者外周血中的 iNKT 细胞。
在首次血液透析(HD)前,急性肾衰竭患者中发现 iNKT 淋巴细胞明显减少。接受 HD 或 PD 的终末期肾脏病患者中耗尽了 iNKT 细胞。HD 后,iNKT 细胞的耗竭更为明显。非透析依赖性慢性肾脏病患者的程度较轻。肾功能不全时 CD56 和 CD161 NK 细胞标记物表达减少。CD56(+)和 CD161(+)iNKT 细胞产生的干扰素-γ多于同一供体的阴性细胞。在肾移植后的第一年,iNKT 细胞及其 NK 细胞标记物的减少得到了逆转。
我们首次描述了 iNKT 淋巴细胞在终末期肾脏病中减少,并通过 HD 进一步耗竭。iNKT 细胞对早期宿主反应很重要,包括其他免疫细胞的激活,其耗竭可能导致肾脏疾病中的免疫功能障碍。