Restored Function of HBV-Specific T Cells after Long-Term Effective Therapy with

StephenW

Gastroenterology. 2012 Jul 12. [Epub ahead of print]
Restored Function of HBV-Specific T Cells after Long-Term Effective Therapy with Nucleos(t)ide Analogues.
Boni C, Laccabue D, Lampertico P, Giuberti T, Viganò M, Schivazappa S, Alfieri A, Pesci M, Gaeta GB, Brancaccio G, Colombo M, Missale G, Ferrari C.
Source
Laboratory of Viral Immunopathology,Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.

Abstract
BACKGROUND & AIMS: In patients with chronic hepatitis B virus (HBV) infection, persistent exposure to high concentrations of antigen can disrupt T-cell functions. It is not clear to what extent long-term suppression of HBV by nucleos(t)ide analogues can restore anti-viral T cell functions. We compared HBV-specific T-cell responses of patients treated with nucleos(t)ide analogues with those detected in other conditions of HBV control.
METHODS: We analyzed intracellular levels of interferon-γ, interleukin-2, and tumor necrosis factor (TNF)-α in HBV-specific T cells following 10 days stimulation with peptides covering the overall HBV genotype D sequence and ex vivo with selected CD8 epitopes and the corresponding HLA-A2 dextramers. Findings from patients treated with nucleos(t)ide analogues who had complete (HBV DNA-/anti-HBs+) or partial (HBV DNA-/HBsAg+) control of their infections were compared with those of patients with spontaneous or IFN-α-induced resolution of acute or chronic infections, inactive HBV carriers, or untreated hepatitis B e antigen-negative patients with chronic infections.
RESULTS: Although HBV-specific T cells from nucleos(t)ide analogue-treated patients with complete control of infection were dysfunctional ex vivo, they had efficient responses after in vitro expansion. These responses were comparable to those of patients who spontaneously resolved acute HBV infection. Nucleos(t)ide analogue-treated patients who were HBV DNA negative but hepatitis B surface antigen positive had lower levels of T-cell responses, but responses greater than those of untreated patients with chronic infection.
CONCLUSIONS: In vitro reactivity can be restored to T cells from patients with suppressed HBV infection following long-term treatment with nucleos(t)ide analogues, despite prolonged exposure to large loads of antigen. Immune therapies that increase the antiviral T-cell response might increase the likelihood of complete HBV control in patients undergoing long-term nucleos(t)ide analogue treatment.

StephenW

胃肠病学。 2012年七月12。 [出处提前打印]
经过长期有效的治疗与核苷（酸）IDE类似物HBV特异性T细胞的功能恢复。
博尼，Laccabueð，Lampertico带够，Giubertiţ，维加诺中号，小号Schivazappa，阿尔菲一个，中号佩西，加埃塔GB，BrancaccioĞ，中号科伦坡，MissaleĞ，法拉利C.
源

病毒免疫病理重点实验室，传染病和肝病Azienda Ospedaliero Universitaria帕尔马，帕尔马，意大利的单位。
抽象
背景与目的：

在慢性乙型肝炎病毒（HBV）感染的患者，持续暴露在高浓度的抗原可以破坏T细胞的功能。目前尚不清楚何种程度上可以恢复长期抑制乙肝病毒的核苷（酸）IDE类似物抗病毒T细胞功能。我们比较核苷（酸）IDE在检测乙肝病毒控制的其他条件的类似物治疗的患者HBV特异性T细胞的反应。
方法：

我们分析了10天刺激涵盖整体HBV D基因型序列和体外与选定的CD8抗原表位肽和细胞水平的γ-干扰素，白细胞介素2，在HBV特异性T细胞和肿瘤坏死因子（TNF）-α相应的，HLA-A2 dextramers。结果从核苷（酸）IDE类似物有治疗的患者（乙肝病毒DNA-/anti-HBs +）或部分（乙肝DNA-/HBsAg +）控制其感染的患者进行了比较自发或IFN-α诱导急性或慢性感染，不活跃的乙肝病毒携带者，或未经治疗乙型肝炎e抗原阴性慢性感染患者的决议。
结果：

虽然从核苷（酸）IDE模拟处理与患者完全控制感染HBV特异性T细胞是体内功能失调，他们有高效的反应，在体外扩增后。这些反应与自发解决急性HBV感染的患者。核苷（酸）IDE类似物治疗的患者HBV DNA阴性，但乙肝表面抗原阳性的T细胞反应水平较低，但比未经治疗的患者与慢性感染者的反应。
结论：

可以恢复到与抑制乙型肝炎病毒感染的患者，核苷（酸）IDE类似物长期治疗后的T细胞在体外的反应，但长时间暴露在大负荷的抗原。增加抗病毒药物的T细胞反应的免疫疗法，在经历长期的核苷（酸）IDE类似物治疗的患者可能会增加完整的乙肝病毒控制的可能性。

咬牙硬挺

上来一次都是运气啊。感谢分享