Hamzaoui Kamel, Kamoun Mariam, Houman Habib, Hentati Fayçal, Hamza M'Hamed, Ayed Khaled, Hamzaoui Agnes
Homeostasis and Cell Dysfunction Unit Research 99/UR/08-40, Medicine University Tunis, 15, Rue Djebel Lakdar 1007 Tunis, Tunisia.
J Neuroimmunol. 2006 Jun;175(1-2):160-8. doi: 10.1016/j.jneuroim.2006.02.011. Epub 2006 Apr 19.
The precise role of natural killer T (NKT) cells in the pathogenesis of Behçet's disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42BD patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients (median: 0.06%; range: 0%-0.3%) when compared to healthy controls (median: 0.23%; range: 0.1%-0.7%; P<0.01). NKT cells were biased toward a Th(1)-like phenotype, with a significant decrease of IL-4/IFN-gamma ratio in BD (median: 0.049; range: 0.01-0.13) vs. healthy controls (median: 0.82; range: 0.4-1.33; P<0.01). NKT cells were increased in CSF-BD samples (median: 0.18%; range: 0.1%-0.4%), when compared to CSF-NIND patients (median: 0.05%; range: 0.01%-0.09%; P<0.01). Based on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide (alpha-GalCer), 80% of BD patients were non-responsive. At the opposite, the reactivity of NKT cells in CSF from BD patients was not impaired. BD-CSF NKT cells exhibited an increased expression of IFN-gamma-producing cells, demonstrating that CSF-NKT cells were functional, and biased toward a Th(1)-like phenotype. These data suggest that functional NKT cells are recruited into BD inflammatory sites contributing to BD pathogenesis.
自然杀伤性T（NKT）细胞在白塞病（BD）发病机制中的精确作用尚不清楚。对42例BD患者外周血单个核细胞（PBMC）以及9例神经BD患者脑脊液（CSF）样本中的NKT细胞频率、细胞因子谱和异质性进行了研究。流式细胞术显示，与健康对照相比，BD患者PBMC中NKT细胞频率降低（中位数：0.06%；范围：0%-0.3%）（健康对照中位数：0.23%；范围：0.1%-0.7%；P<0.01）。BD患者的NKT细胞倾向于Th(1)样表型，BD患者IL-4/IFN-γ比值显著降低（中位数：0.049；范围：0.01-0.13），而健康对照为（中位数：0.82；范围：0.4-1.33；P<0.01）。与CSF-非神经系统疾病（NIND）患者相比，CSF-BD样本中NKT细胞增加（中位数：0.18%；范围：0.1%-0.4%）（CSF-NIND患者中位数：0.05%；范围：0.01%-0.09%；P<0.01）。基于PBMC来源的NKT细胞对α-半乳糖神经酰胺（α-GalCer）的反应性，80%的BD患者无反应。相反，BD患者CSF中NKT细胞的反应性未受损。BD-CSF NKT细胞中产生IFN-γ的细胞表达增加，表明CSF-NKT细胞具有功能，且倾向于Th(1)样表型。这些数据表明，功能性NKT细胞被募集到BD炎症部位，参与BD的发病机制。
