Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma
Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma
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DOI：
10.1016/j.hepres.2005.02.008
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发表时间：
2005-08-01
影响因子：
4.2
通讯作者：
Kakumu, S
中科院分区：
文献类型：
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作者：
Okumura, A;Ishikawa, T;Kakumu, S
自然杀伤 T (NKT) 细胞具有经典 T 细胞和 NK 细胞的特征。 NKT 是异质群体，识别与 CD1d 分子相关的糖脂。我们调查了 14 名健康受试者和丙型慢性肝炎（CH；14 例）和肝细胞癌（HCC；13 例）治疗期间患者的 Th1/Th2 细胞因子产生以及循环 NKT 细胞的频率和表型。分别在CH和HCC的干扰素(IFN)/利巴韦林和射频消融治疗前和2周后获得外周血单核细胞(PBMC)。将 PBMC 与 α-半乳糖苷 (α-GalCer) 和白细胞介素 2 (IL-2) 一起培养 10 天。使用流式细胞术分析 NKT 细胞的频率和 IFN-γ/IL-4 产生。对七名慢性肝炎患者的肝活检标本的肝内淋巴细胞进行了分析。对于对照组，循环 V α 24+CD3+ T 细胞的流行率为 PBMC 的 0.9 +/- 0.9%，并且响应 α-GalCel 增加至 8.5 +/- 8.9% (p < 0.00 1)。 CH 中也注意到类似的频率和扩展。治疗期间频率增加。与对照组相比，HCC 的患病率往往较高，并且对 α-GalCel 的反应良好。尽管所有组中 V α 24+V β 11+CD3+ T 细胞的频率较低，但分布模式与 V α 24+V β 11-CD3+ T 细胞相似。尽管对 α-GalCel 的反应并未受损，但与对照组的 5.0 +/- 4.0% 相比，CH 中 CD56+CD3+ T 细胞的患病率（独立于治疗）较低（2-3%）。 V α 24+CD3+T 细胞的 IFN-γ 产生在各组之间没有差异，但在治疗后变得更高，而 IL-4 产生降低。肝脏中 NKT 群体的频率高于外周血中的频率。我们的研究表明，CD1d 反应性 T 细胞在不同人群中具有不同的分布，并且患者的治疗会改变 NKT 细胞的细胞因子反应。 (c) 2005 Elsevier B.V. 保留所有权利。
Natural killer T (NKT) cells share features of both classical T cells and NK cells. NKT are heterogenous populations, and recognize glycolipids associated with CD1d molecule. We investigated Th1/Th2 cytokine production as well as frequency and phenotype of circulating NKT cells in 14 healthy subjects and in patients during therapy with type C chronic hepatitis (CH; 14 cases) and hepatocellular carcinoma (HCC; 13 cases). Peripheral blood mononuclear cells (PBMC) were obtained before and 2 weeks later interferon (IFN)/ribavirin and radiofrequency ablation therapy for CH and HCC, respectively. PBMC were cultured for 10 days with alpha-galactosylceran-fide (alpha-GalCer) and interleukin-2 (IL-2). Frequencies and IFN-gamma/IL-4 production of NKT cells were analyzed using flow cytometry. Intrahepatic lymphocytes were analyzed in seven CH patients with liver biopsy specimen. Prevalence of circulating V alpha 24+CD3+ T cells was 0.9 +/- 0.9% of PBMC for controls and increased to 8.5 +/- 8.9% (p < 0.00 1) in response to alpha-GalCel. Similar frequency and expansion were noted in CH. The frequency increased during therapy. The prevalence in HCC tended to be high compared to controls and response to alpha-GalCel was well. Although frequency of V alpha 24+V beta 11+CD3+ T cells was low in all groups, the distribution pattern was similar to V alpha 24+V beta 11-CD3+ T cells. Prevalence of CD56+CD3+ T cells was low independent of therapy in CH (2-3%) compared to 5.0 +/- 4.0% of controls, although response to alpha-GalCel was not impaired. IFN-gamma production of V alpha 24+CD3+T cells did not differ among groups, but became greater after treatment in contrast to lowered IL-4 production. Frequencies of NKT populations were higher in liver than in peripheral blood. Our study suggests that CD1d-reactive T cells have distinct distribution in different populations and therapy for patients alters cytokine response of NKT cells. (c) 2005 Elsevier B.V. All rights reserved.