Kojo S, Adachi Y, Keino H, Taniguchi M, Sumida T
University of Tsukuba, Ibaraki, Japan.
Arthritis Rheum. 2001 May;44(5):1127-38. doi: 10.1002/1529-0131(200105)44:5<1127::AID-ANR194>3.0.CO;2-W.
We examined the reduction of T cell receptor (TCR) AV24+,BV11+ CD4-,CD8- (double-negative [DN]) natural killer T (NKT) cells in peripheral blood lymphocytes (PBLs) from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjogren's syndrome (SS) to analyze why NKT cells are selectively reduced in autoimmune diseases, and to examine whether nonresponse to alpha-galactosylceramide (alpha-GalCer) is due to an abnormality in the antigen-presenting cells (APCs) or NKT cells.
Peripheral blood from patients with RA (n = 20), SLE (n = 18), SSc (n = 13), and SS (n = 17), as well as from healthy donors (n = 13) and patients with Behçet's disease (BD; n = 20), was examined by flow cytometry to determine the number of TCR AV24+,BV11+ DN T cells. PBLs from 10 RA, 10 SLE, 8 SSc, and 9 SS patients, as well as from 7 healthy subjects, were cultured in vitro with alpha-GalCer, and the number of TCR AV24+,BV11+ DN NKT cells was estimated. APCs from responder and nonresponder patients were cocultured with NKT cells from responder and nonresponder patients.
The mean +/- SEM number of TCR AV24+,BV11+ DN NKT cells per ml of whole blood was found to be 48.8+/-10.0 in RA patients, 50.6+/-12.9 in SLE patients, 80.8+/-30.6 in SSc patients, and 40.0+/-11.7 in SS patients, while 290.0+/-69.6 and 321.2+/-103.4 NKT cells were present in healthy subjects and BD patients, respectively (P < 0.01). Three of 10 RA patients, 5 of 10 SLE patients, 4 of 8 SSc patients, and 6 of 9 SS patients (a total of 18 of 37 patients, or 48.6%) responded to alpha-GalCer, indicating that patients could be divided into two groups: alpha-GalCer responders and nonresponders. In contrast, NKT cells from all healthy subjects proliferated against alpha-GalCer. APCs from all nonresponder patients were found to function as alpha-GalCer-presenting cells, while NKT cells from nonresponders did not expand even in the presence of APCs from normal responders.
These findings strongly suggest that patients with autoimmune diseases can be divided into two groups (alpha-GalCer responders and nonresponders). They also suggest that the reduced numbers of NKT cells in patients with autoimmune diseases may be due to an inadequate amount of alpha-GalCer-like natural ligands (i.e., adequate in only 48.6% of patients) for the induction of NKT cells in vivo, or to a dysfunction in the NKT cells themselves (in 51.4% of patients).
我们检测了类风湿关节炎（RA）、系统性红斑狼疮（SLE）、系统性硬化症（SSc）和干燥综合征（SS）患者外周血淋巴细胞（PBL）中T细胞受体（TCR）AV24 +、BV11 + CD4 -、CD8 -（双阴性[DN]）自然杀伤T（NKT）细胞的减少情况，以分析自身免疫性疾病中NKT细胞选择性减少的原因，并研究对α-半乳糖神经酰胺（α-GalCer）无反应是否归因于抗原呈递细胞（APC）或NKT细胞异常。
通过流式细胞术检测RA（n = 20）、SLE（n = 18）、SSc（n = 13）和SS（n = 17）患者以及健康供者（n = 13）和白塞病（BD；n = 20）患者外周血中TCR AV24 +、BV11 + DN T细胞的数量。将10例RA、10例SLE、8例SSc和9例SS患者以及7例健康受试者的PBL与α-GalCer在体外培养，并估计TCR AV24 +、BV11 + DN NKT细胞的数量。将反应者和无反应者患者的APC与反应者和无反应者患者的NKT细胞共培养。
每毫升全血中TCR AV24 +、BV11 + DN NKT细胞的平均±标准误数量在RA患者中为48.8±10.0，SLE患者中为50.6±12.9，SSc患者中为80.8±30.6，SS患者中为40.0±11.7，而健康受试者和BD患者中分别有290.0±69.6和321.2±103.4个NKT细胞（P < 0.01）。10例RA患者中有3例、10例SLE患者中有5例、8例SSc患者中有4例、9例SS患者中有6例（37例患者中共18例，即48.6%）对α-GalCer有反应，这表明患者可分为两组：α-GalCer反应者和无反应者。相比之下，所有健康受试者的NKT细胞对α-GalCer均有增殖反应。发现所有无反应者患者的APC均作为α-GalCer呈递细胞发挥作用，而无反应者的NKT细胞即使在存在正常反应者的APC时也不扩增。
这些发现强烈表明自身免疫性疾病患者可分为两组（α-GalCer反应者和无反应者）。它们还表明自身免疫性疾病患者中NKT细胞数量减少可能是由于体内诱导NKT细胞的α-GalCer样天然配体数量不足（即仅48.6%的患者足够），或由于NKT细胞自身功能障碍（51.4%的患者）。
