Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human mid tetramer
Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human mid tetramer
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DOI：
10.1053/gast.2002.36020
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发表时间：
2002-10-01
期刊：
影响因子：
29.4
通讯作者：
Gershwin, ME
中科院分区：
文献类型：
--
作者：
Kita, H;Naidenko, OV;Gershwin, ME
背景和目标：自然杀伤T（NKT）细胞是淋巴细胞的一个亚群，其在先天免疫应答的调节和自身免疫的发展中起重要作用。然而，只有有限的研究试图量化自身免疫性疾病中NKT细胞的数量，特别是因为与该亚群的定义相关的困难。研究方法：我们使用了由杆状病毒表达的重组CD 1d蛋白与α-半乳糖神经酰胺（α-GalCer）复合产生的人CD 1d（hCD 1d）四聚体，并定量了对照组和原发性胆汁性肝硬化（PBC）患者血液和肝脏中的hCD 1d四聚体反应细胞。结果：大多数CD 1d-alphaGalCer限制性NKT细胞对TCR Valpha 24和V β 11呈阳性。除了CD 4（-）CD 8（-）和CD 4（+）CD 8-细胞群外，CD 1d-alphaGalCer限制性NKT细胞中还存在不同的CD 4（-）CD 8（+）细胞群。在健康个体的血液和肝脏中，CD 1d-alphaGalCer限制性NKT细胞的频率相似。相比之下，PBC患者肝脏中CD 1d-alphaGalCer限制性NKT细胞的频率显著高于血液。PBC患者肝脏中CD 1d-α-GalCer限制性NKT细胞的频率也显著高于健康个体。结论：这种细胞的频率和功能不仅应在血液中进行研究，还应在自身免疫性疾病的靶器官中进行研究。在PBC中观察到CD 1d-alphaGalCer限制性NKT细胞在炎症部位的选择性富集，表明这些细胞在PBC发展中的作用。
Background & Aims: Natural killer T (NKT) cells are a subset of lymphocytes incriminated in playing an important role in the modulation of the innate immune response and the development of autoimmunity. However, there have been only limited studies attempting to quantitate the number of NKT cells in autoimmune disease, particularly because of difficulties associated with definition of this subpopulation. Methods: We used a human CD1d (hCD1d) tetramer produced by a baculovirus expressing recombinant CD1d protein complexed with alpha-galactosylceramide (alpha-GalCer) and quantitated hCD1d tetramer reactive cells in blood and liver from controls and patients with primary biliary cirrhosis (PBC). Results: The majority of CD1d-alphaGalCer-restricted NKT cells were positive for TCR Valpha24 and Vbeta11. There was a distinct CD4(-) CD8(+) population within the CD1d-alphaGalCer-restricted NKT cells in addition to the CD4(-) CD8(-) and CD4(+) CD8- population. The frequency of CD1d-alphaGalCer-restricted NKT cells was similar between blood and liver in healthy individuals. In contrast, the frequency of CD1d-alphaGalCer-restricted NKT cells in the liver was significantly higher than in the blood of PBC patients. The frequency of CD1d-alpha-GalCer-restricted NKT cells in the liver was also significantly higher in PBC patients than in healthy individuals. Conclusions: The frequency and function of such cells should be studied not only in blood but also in the target organ of the autoimmune disease. Selective enrichment of CD1d-alphaGalCer-restricted NKT cells at the site of inflammation is observed in PBC, suggesting a role of these cells in the development of PBC.