Department of Infectious Diseases, the Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, P.R. China.
Viral Immunol. 2011 Aug;24(4):303-10. doi: 10.1089/vim.2010.0135. Epub 2011 Jul 1.
Both T-helper 17 cells (Th-17) and CD4(+)CD25(+) regulatory T cells (Tregs) play important roles in the pathogenesis of hepatitis B virus (HBV) infection. Recent studies have suggested that Th-17 and Treg cells are increased in patients with chronic hepatitis B (CHB). This study further characterizes Th-17 and Treg cells in the blood of HBV-associated acute-on-chronic liver failure (ACLF) patients, and aids our understanding of how the two subsets of CD4(+) T cells affect each other and contribute to survival. Blood samples were obtained from 30 patients with HBV-associated ACLF, 30 patients with CHB, and 30 normal controls (NC). The frequencies of Th-17 and Treg cells were determined by intracellular cytokine staining analysis. To observe the suppressive function of Tregs, purified CD4(+)CD25(+) Tregs from peripheral blood mononuclear cells (PBMCs) were co-cultured with CD4(+)CD25(-) T cells for 48 h, and then IFN-γ and IL-17A from the supernatants were measured by ELISA. We found that both Th-17 and FoxP3(+) Treg cells were increased in ACLF patients. IL-17A secretion by CD4(+) T cells was not regulated by Treg cells, even though Tregs exhibited significant inhibition of IFN-γ production. Most importantly, the ratio of Th-17 to Treg cells was associated inversely with the survival of ACLF patients. These findings provide new information regarding the pathogenesis of HBV-associated ACLF, and the ratio of Th-17 to Tregs may represent a potential prognostic marker for the disease.
辅助性 T 细胞 17(Th17)和 CD4+CD25+调节性 T 细胞(Treg)在乙型肝炎病毒(HBV)感染的发病机制中起重要作用。最近的研究表明,慢性乙型肝炎(CHB)患者的 Th17 和 Treg 细胞增加。本研究进一步描述了 HBV 相关慢加急性肝衰竭(ACLF)患者血液中的 Th17 和 Treg 细胞,并帮助我们了解这两个 CD4+T 细胞亚群如何相互影响并有助于生存。采集了 30 例 HBV 相关 ACLF 患者、30 例 CHB 患者和 30 例正常对照(NC)的血液样本。通过细胞内细胞因子染色分析确定 Th17 和 Treg 细胞的频率。为了观察 Treg 的抑制功能,从外周血单个核细胞(PBMCs)中纯化 CD4+CD25+Treg 与 CD4+CD25-T 细胞共培养 48 小时,然后通过 ELISA 测量上清液中的 IFN-γ和 IL-17A。我们发现 ACLF 患者的 Th17 和 FoxP3+Treg 细胞均增加。CD4+T 细胞的 IL-17A 分泌不受 Treg 细胞调节,尽管 Treg 细胞对 IFN-γ的产生表现出明显的抑制作用。最重要的是,Th17 与 Treg 细胞的比例与 ACLF 患者的生存呈负相关。这些发现为 HBV 相关 ACLF 的发病机制提供了新信息,Th17 与 Treg 细胞的比例可能是该疾病的潜在预后标志物。