Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Rheumatology (Oxford). 2011 Jun;50(6):1054-63. doi: 10.1093/rheumatology/keq457. Epub 2011 Jan 27.
This study was designed to examine the frequency of natural killer T (NKT) cells and the response to α-galactosylceramide (α-GalCer) in SLE patients and to investigate the clinical relevance of NKT cell levels.
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 α-GalCer. Proliferation indices of NKT cells were estimated by flow cytometry.
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 α-GalCer was diminished. This poor responsiveness to α-GalCer was found to be due to NKT cell dysfunction rather than to an abnormality in CD1d-expressing cells.
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.
本研究旨在检测自然杀伤 T（NKT）细胞的频率以及对α-半乳糖神经酰胺（α-GalCer）的反应在系统性红斑狼疮（SLE）患者中的变化，并探讨 NKT 细胞水平的临床相关性。
本研究纳入了 128 例 SLE 患者和 92 名年龄和性别匹配的健康对照者（HCs）。通过流式细胞术检测 NKT 细胞和 CD1d 水平。通过 RT-PCR 测定基因表达，通过多细胞因子测定法测定细胞因子分泌。体外使用 α-GalCer 培养外周血单个核细胞（PBMCs）。通过流式细胞术评估 NKT 细胞的增殖指数。
与 HCs 相比，SLE 患者外周血中 NKT 细胞的百分比和绝对数明显较低，而 PBMCs 中的 CD1d 水平在两组之间无差异。值得注意的是，这种 NKT 细胞缺乏与 SLEDAI 相关。发现 SLE 患者的 NKT 细胞增殖受损，且 NKT 细胞对 α-GalCer 的细胞因子产生减少。这种对 α-GalCer 的反应不良被认为是由于 NKT 细胞功能障碍而不是 CD1d 表达细胞的异常所致。
我们的数据表明，SLE 患者的 NKT 细胞水平和功能存在缺陷。此外，这些缺陷与疾病活动度相关。这些 NKT 细胞异常似乎可能导致 SLE 中免疫系统失调。
