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慢性丙型肝炎活动期患者调节性 T 细胞频率和功能升高。

Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C.

机构信息

Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan.

出版信息

J Gastroenterol. 2012 Jul;47(7):823-33. doi: 10.1007/s00535-012-0544-9. Epub 2012 Feb 28.

DOI:10.1007/s00535-012-0544-9
PMID:22367277
Abstract

BACKGROUND

Regulatory T cells (Tregs) play a pivotal role in the persistence of hepatitis C virus infection. The aim of this study was to evaluate the frequency and function of Tregs in patients with chronic hepatitis C (CHC).

METHODS

We enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14 age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+, CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence-activated cell sorting (FACS). The frequency of Tregs was determined by calculating the percentage of CD4+CD25(high) T cells among CD4 T cells. CD127 and CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming growth factor (TGF)-β and interleukin (IL)-10 in immunosuppressive assays were detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive abilities of Tregs were evaluated by measuring their ability to inhibit the proliferation of effector cells.

RESULTS

Higher proportions of Tregs were found in the CH and PNALT groups compared with the HS group. The populations of CD127 low/negative and CD45RA negative cells were higher in the CH group than in the PNALT group. The expressions of IL-10 and TGF-β in the CH and PNALT groups were significantly higher than those in the HS group. In addition, the immunosuppressive ability of Tregs from the CH group was increased relative to that in the PNALT and the HS group.

CONCLUSIONS

CHC patients, irrespective of liver function, had higher frequencies of Tregs than healthy subjects; however, only CHC patients with inflammation showed enhanced immunosuppressive function of Tregs.

摘要

背景

调节性 T 细胞(Tregs)在丙型肝炎病毒感染的持续存在中发挥关键作用。本研究旨在评估慢性丙型肝炎(CHC)患者 Tregs 的频率和功能。

方法

我们纳入了 44 例丙氨酸氨基转移酶(ALT)升高的 CHC 患者(CH 组)、13 例持续正常 ALT 水平的 CHC 患者(PNALT 组)和 14 名年龄匹配的健康受试者(HS 组;对照组)。采用三色荧光激活细胞分选(FACS)鉴定 Tregs 为 CD4+、CD25+和叉头框 P3(Foxp3)+T 淋巴细胞。通过计算 CD4+T 细胞中 CD4+CD25(高)T 细胞的百分比来确定 Tregs 的频率。还分析了 Tregs 的亚群 CD127 和 CD45RA。采用酶联免疫吸附试验(ELISA)检测免疫抑制试验中血清转化生长因子(TGF)-β和白细胞介素(IL)-10 的水平。通过测量 Tregs 抑制效应细胞增殖的能力来评估 Tregs 的免疫抑制能力。

结果

CH 和 PNALT 组的 Tregs 比例高于 HS 组。CH 组的 CD127 低/阴性和 CD45RA 阴性细胞群高于 PNALT 组。CH 和 PNALT 组的 IL-10 和 TGF-β表达明显高于 HS 组。此外,CH 组 Tregs 的免疫抑制能力相对于 PNALT 和 HS 组有所增加。

结论

无论肝功能如何,CHC 患者的 Tregs 频率均高于健康受试者;然而,只有炎症性 CHC 患者的 Tregs 表现出增强的免疫抑制功能。

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