Sprinzl M F, Russo C, Kittner J, Allgayer S, Grambihler A, Bartsch B, Weinmann A, Galle P R, Schuchmann M, Protzer U, Bauer T
Institute of Virology, Technische Universität München / Helmholtz Zentrum München, Munich, Germany; Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
J Viral Hepat. 2014;21(9):633-41. doi: 10.1111/jvh.12189. Epub 2013 Nov 19.
The effect of pegylated interferon-α (IFN) add-on therapy on HBV-specific T-cell responses was evaluated in 12 patients with stable, undetectable hepatitis B virus (HBV) load under nucleos(t)ide analogue therapy. Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, 24 and 48 of IFN add-on therapy. Quantity and quality of circulating HBV S- and core-specific CD4 and CD8 T cells were analysed ex vivo by flow cytometry. HBV S- and core-specific CD4 T-cell numbers modestly increased within 8 weeks of IFN administration (P = 0.0391 and P = 0.0195), whereas HBV-specific CD8 T cells in general showed only minor changes under IFN add-on therapy. Functionality of HBV-specific CD4 but not CD8 T cells positively correlated with serum transaminase activity. In addition, we observed an increase in CD4 T cells producing tumour necrosis factor-α (TNFα) without antigen restimulation (P = 0.0039), which correlated with elevated transaminases. During IFN add-on therapy, two patients developed an anti-HBs seroconversion, only one of whom showed a relevant increase in HBV-specific T cells. In conclusion, IFN add-on therapy of chronic hepatitis B increased HBV-specific T-cell responses and affected a previously unrecognized TNFα-monofunctional CD4 T-cell population. Although the observed T-cell responses did not correlate with HBsAg seroconversion, we expect additional insights into the immunopathogenesis of hepatitis B, following the characterization of the newly identified TNF α-monofunctional T-cell population.
在12例接受核苷（酸）类似物治疗且乙肝病毒（HBV）载量稳定且不可检测的患者中，评估了聚乙二醇化干扰素-α（IFN）联合治疗对HBV特异性T细胞反应的影响。在IFN联合治疗的第0、4、8、12、24和48周分离外周血单个核细胞。通过流式细胞术体外分析循环中HBV S抗原和核心抗原特异性CD4和CD8 T细胞的数量和质量。在给予IFN的8周内，HBV S抗原和核心抗原特异性CD4 T细胞数量适度增加（P = 0.0391和P = 0.0195），而在IFN联合治疗下，HBV特异性CD8 T细胞总体上仅显示出微小变化。HBV特异性CD4而非CD8 T细胞的功能与血清转氨酶活性呈正相关。此外，我们观察到在无抗原再刺激的情况下，产生肿瘤坏死因子-α（TNFα）的CD4 T细胞增加（P = 0.0039），这与转氨酶升高相关。在IFN联合治疗期间，两名患者发生了抗-HBs血清学转换，其中只有一名患者的HBV特异性T细胞有相关增加。总之，慢性乙型肝炎的IFN联合治疗增加了HBV特异性T细胞反应，并影响了先前未被认识的TNFα单功能CD4 T细胞群体。尽管观察到的T细胞反应与HBsAg血清学转换无关，但我们期望在新鉴定的TNFα单功能T细胞群体的特征描述之后，能对乙型肝炎的免疫发病机制有更多深入了解。
