Regulatory Role of CD4+CD25+Foxp3+ Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients
Regulatory Role of CD4+CD25+Foxp3+ Regulatory T Cells on IL-17-Secreting T Cells in Chronic Hepatitis B Patients
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DOI：
10.1007/s10620-013-3022-1
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Chen, Zhi
中科院分区：
文献类型：
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作者：
Li, Jie;Shi, Jun;Chen, Zhi
在慢性B型肝炎（CH B）患者中，分泌白细胞介素（IL）-17的CD 4（+）T（Th 17）和CD 4（+）CD 25（+）Foxp 3（+）T调节（Treg）细胞均与疾病进展或肝损伤相关。为了解Treg细胞和IL-17分泌性T细胞在B肝炎病毒（HBV）感染中的相互关系，采用流式细胞术检测了HBeAg阳性的CHB患者和健康对照者中Treg细胞和IL-17分泌性T细胞的比例。通过从HBeAg阳性CHB患者的外周血单核细胞（PBMC）中去除Treg细胞来确定Treg细胞对Ag特异性IL-17分泌性T细胞分化的作用。（1.71 +/- A 0.58对比1.08 +/- A 0.36%; P < 0.01）和Treg细胞（8.92 +/- A 4.11 vs. 6.45 +/- A 1.56%; HBeAg阳性的CHB患者外周血IL-17分泌型CD 8（+）T（Tc 17）细胞较正常对照组明显增高（P < 0.01），但IL-17分泌型CD 8（+）T（Tc 17）细胞无明显变化。CHB患者Treg细胞频率与Th 17细胞频率显著相关（r = 0.625，P = 0.001）。斯皮尔曼分析显示Treg细胞频率与HBV DNA载量呈正相关（r = 0.508，P = 0.008），Th 17细胞频率与血清丙氨酸氨基转移酶水平呈正相关（r = 0.516，P = 0.007）。Treg细胞的缺失显著增强了重组HBV核心抗原刺激后PBMC中Th 17和Tc 17细胞的发育，我们的数据表明Th 17细胞和Treg细胞之间存在明显的负相关关系，Treg细胞可以抑制CHB患者Th 17细胞的发育。
Both interleukin (IL)-17-secreting CD4(+) T (Th17) and CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells have been shown to be associated with disease progression or liver damage in chronic hepatitis B (CHB) patients. However, the relationship between Treg cells and IL-17-secreting T cells in hepatitis B virus (HBV) infections is unclear.The frequencies of Treg cells and IL-17-secreting T cells in hepatitis B e antigen (HBeAg)-positive CHB patients and healthy subjects were measured by flow cytometric analysis. The role of Treg cells on the differentiation of Ag-specific IL-17-secreting T cells was determined by removing the Treg cells from peripheral blood mononuclear cells (PBMCs) in HBeAg-positive CHB patients.The frequencies of both Th17 (1.71 +/- A 0.58 vs. 1.08 +/- A 0.36 %; P < 0.01) and Treg cells (8.92 +/- A 4.11 vs. 6.45 +/- A 1.56 %; P < 0.01) were increased in the peripheral blood of HBeAg-positive CHB patients compared with healthy controls, but in not the IL-17-secreting CD8(+) T (Tc17) cells. The frequency of Treg cells was significantly associated with that of Th17 cells (r = 0.625, P = 0.001) in CHB patients. Spearman analysis showed a positive correlation between the frequency of Treg cells and HBV DNA load (r = 0.508, P = 0.008), as well as between the frequency of Th17 cells and serum alanine aminotransferase level (r = 0.516, P = 0.007). The deletion of Treg cells significantly enhanced both Th17 and Tc17 cell development in PBMCs following recombinant HBV core antigen stimulation.Our data indicate a clear inverse relationship between Th17 cells and Treg cells and that Treg cells can inhibit Th17 cell development in CHB patients.