Wang Yingxue, Hu Xiaojing, Guo Chengshan, Zhang Qi, Peng Jun, Zhang Jianhua, Li Lizhen, Zhang Ti, Xu Conggao
Hematology Research Laboratory, Qilu Hospital, Shandong University, Jinan, China.
Acta Haematol. 2008;119(3):178-86. doi: 10.1159/000137501. Epub 2008 Jun 6.
Natural killer T (NKT) cells play an important role in the regulation of immune responses in a broad range of diseases, including autoimmune disorders, infectious diseases and cancer. So far, few studies have evaluated the roles of NKT cells in the pathogenesis of aplastic anemia (AA), an autoimmune disease. In this study, we investigated the quantitative and qualitative changes in NKT cells in bone marrow (BM) mononuclear cells of AA patients in response to in vitro stimulation with alpha-galactosylceramide. Compared to healthy controls, BM from AA patients had reduced fraction of NKT cells, which possessed a decreased potential to expand in vitro in response to alpha-galactosylceramide stimulation, producing more IFNgamma+ NKT1 cells. In the presence of rhG-CSF, the expansion capacity of NKT cells stimulated by alpha-galactosylceramide was significantly reduced in both AA and control groups, with the majority of the activated NKT cells expressing intracellular IL-4, and the fractions of IFNgamma+ NKT cells were significantly reduced. In summary, our results indicate that polarization of NKT cells towards the NKT2 subpopulation occurs after co-stimulation with alpha-galactosylceramide and rhG-CSF in AA.
自然杀伤T(NKT)细胞在多种疾病(包括自身免疫性疾病、传染病和癌症)的免疫反应调节中发挥重要作用。到目前为止,很少有研究评估NKT细胞在再生障碍性贫血(AA,一种自身免疫性疾病)发病机制中的作用。在本研究中,我们调查了AA患者骨髓(BM)单个核细胞中NKT细胞在体外经α-半乳糖神经酰胺刺激后的数量和质量变化。与健康对照相比,AA患者的骨髓中NKT细胞比例降低,其在体外对α-半乳糖神经酰胺刺激的扩增潜力下降,产生更多的IFNγ+ NKT1细胞。在重组人粒细胞集落刺激因子(rhG-CSF)存在的情况下,α-半乳糖神经酰胺刺激的NKT细胞在AA组和对照组中的扩增能力均显著降低,大多数活化的NKT细胞表达IL-4,IFNγ+ NKT细胞比例显著降低。总之,我们的结果表明,在AA中,NKT细胞在与α-半乳糖神经酰胺和rhG-CSF共同刺激后向NKT2亚群极化。