Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity
Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity
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DOI：
10.1093/rheumatology/keq457
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发表时间：
2011-06-01
期刊：
影响因子：
5.5
通讯作者：
Park, Yong-Wook
中科院分区：
文献类型：
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作者：
Cho, Young-Nan;Kee, Seung-Jung;Park, Yong-Wook
Objective.本研究旨在检测SLE患者自然杀伤T（NKT）细胞的频率和对α-半乳糖神经酰胺（α-GalCer）的反应，并探讨NKT细胞水平的临床相关性。SLE患者（n = 128）和年龄和性别匹配的健康对照（HC）（n = 92）入选本研究。流式细胞仪检测NKT细胞和CD 1d水平。RT-PCR法检测基因表达，多细胞因子法检测细胞因子分泌。用α-GalCer体外培养外周血单核细胞（PBMC）。流式细胞仪检测NKT细胞增殖指数。SLE患者外周血中NKT细胞的数量和绝对数显著低于HC，而PBMC中CD 1d水平在这两组之间相当。值得注意的是，发现这种NKT细胞缺乏与SLEDAI相关。发现SLE患者的NKT细胞增殖受损，并且响应于α-GalCer的NKT细胞的细胞因子产生减少。发现这种对α-GalCer的不良反应是由于NKT细胞功能障碍而不是CD 1d表达细胞的异常。我们的数据表明，NKT细胞的水平和功能是有缺陷的SLE患者。此外，发现这些缺陷反映了疾病活动。这些NKT细胞异常可能导致SLE患者免疫系统失调。
Objective. This study was designed to examine the frequency of natural killer T (NKT) cells and the response to alpha-galactosylceramide (alpha-GalCer) in SLE patients and to investigate the clinical relevance of NKT cell levels.Methods. Patients with SLE (n = 128) and age- and sex-matched healthy controls (HCs) (n = 92) were enrolled in the study. NKT cell and CD1d levels were measured by flow cytometry. Gene expression was determined by RT-PCR, and cytokine secretion by multiple cytokine assay. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro with alpha-GalCer. Proliferation indices of NKT cells were estimated by flow cytometry.Results. Percentages and absolute numbers of NKT cells were significantly lower in the peripheral blood of SLE patients than in that of HCs, whereas CD1d levels in PBMCs were comparable between these two groups. Notably, this NKT cell deficiency was found to be correlated with SLEDAI. NKT cell proliferation was found to be impaired in SLE patients, and cytokine production by NKT cells in response to alpha-GalCer was diminished. This poor responsiveness to alpha-GalCer was found to be due to NKT cell dysfunction rather than to an abnormality in CD1d-expressing cells.Conclusions. Our data show that NKT cell levels and functions are defective in SLE patients. Furthermore, these deficiencies were found to reflect disease activity. It would appear that these NKT cell abnormalities could contribute to immune system dysregulation in SLE.