干扰素治疗差异提高先天免疫和适应性抗病毒反应

StephenW

http://www.journal-of-hepatology.eu/article/S0168-8278%2812%2900761-1/abstract?elsca1=etoc&elsca2=email&elsca3=0168-8278_201302_58_2&elsca4=gastroenterology
Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B
聚乙二醇化α-干扰素治​​疗慢性乙型肝炎差异提高先天免疫和适应性抗病毒反应
    Lorenzo Micco    ,    Dimitra Peppa    ,    Elisabetta Loggi    ,    Anna Schurich    ,
    Lucy Jefferson    ,    Carmela Cursaro    ,    Arianna Martello Panno    ,    Mauro Bernardi
    ,    Christian Brander    ,    Florian Bihl    ,    Pietro Andreone    ,    Mala K. Main

Background & Aims

A better understanding of the immunomodulatory effects of PegIFNα therapy could allow more rational optimisation of future therapeutic approaches in chronic HBV infection. In this study, we evaluated dynamic changes in the innate and adaptive arms of the immune system induced by PegIFNα.
Methods

PBMC were obtained from a cohort of patients with eAg-negative CHB before, during and after PegIFNα treatment. The number, phenotype and function of global and virus-specific T cells and NK cells were analyzed by flow cytometry and serum cytokines by ELISA or CBA.
Results

The absolute number of CD8 T cells was strikingly reduced on PegIFNα therapy (p<0.001), with a predominant loss of end-stage effectors, including CMV-specific CD8 T cells. There was no significant recovery of the exhausted HBV-specific CD8 T cell response. By contrast, PegIFNα was able to potently and cumulatively drive the proliferation and expansion in absolute numbers of CD56bright NK cell numbers (p<0.001), with induction of the pro-proliferative cytokine IL-15. Expanded CD56bright NK cells showed enhanced expression of activation markers and the activating receptor NKp46, accompanied by augmentation of TRAIL and IFN-γ expression (p<0.001). Peak virological response (temporal within individual patients and cross-sectional within the cohort) correlated with the degree of expansion of functional CD56bright NK cells.
Conclusions

IFN-α mediates divergent effects on the innate and adaptive arms of the immune system in vivo. The efficacy of PegIFNα may be limited by its depleting effect on CD8 T cells; conversely, it can cumulatively drive proliferation, activation and antiviral potential of CD56bright NK cells.

StephenW

背景与目的

更好地了解PegIFNα治疗具有免疫调节作用，可以让更合理的优化，未来在慢性HBV感染的治疗方法。在这项研究中，我们评估PegIFNα诱导的免疫系统的先天免疫和适应性武器的动态变化。
方法

从队列前的东亚运动会阴性CHB患者PBMC获得PegIFNα治疗，期间和之后。通过ELISA或CBA用流式细胞仪和血清细胞因子的数目，全球和病毒特异性T细胞和NK细胞的表型和功能进行了分析。
结果

PegIFNα治疗（P <0.001），终末期效应的一个主要的损失，包括巨细胞病毒特异性CD8 + T细胞CD8 + T细胞的绝对数量显着降低。精疲力竭的HBV特异性CD8 T细胞的反应没有显着的恢复。与此相反，PegIFNαpotently和累计带动的增殖和扩张的绝对数量CD56bright NK细胞数（P <0.001），与增殖的细胞因子IL-15的诱导。扩大CD56bright NK细胞活化标志物的表达增强和激活受体NKp46，伴随着增强TRAIL和IFN-γ的表达（P <0.001）。峰值的病毒学反应（时间内个别病人和横截面内的队列）与扩展功能CD56bright NK细胞的程度。
结论

IFN-α介导的发散作用，在体内的免疫系统对先天和适应性臂。的疗效PegIFNα其消耗对CD8 + T细胞的影响可能是有限的，相反，它可以累积驱动CD56bright NK细胞的增殖，活化和抗病毒潜力。

咬牙硬挺

感谢分享