在小鼠HBV感染模型中，血清HBsAg清除率对CD8 + T细胞反应的影

StephenW

J Exp Med

. 2020 Nov 2;217(11):e20200298.
doi: 10.1084/jem.20200298.
Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection
Valeria Fumagalli  1   2 , Pietro Di Lucia  1 , Valentina Venzin  1   2 , Elisa B Bono  1 , Robert Jordan  3 , Christian R Frey  3 , William Delaney  3 , Francis V Chisari  4 , Luca G Guidotti  1   2 , Matteo Iannacone  1   2   5
Affiliations
Affiliations

    1
    Division of Immunology, Transplantation and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
    2
    Vita-Salute San Raffaele University, Milan, Italy.
    3
    Gilead Sciences, Foster City, CA.
    4
    Deparment of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA.
    5
    Experimental Imaging Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

    PMID: 32761167 DOI: 10.1084/jem.20200298

Abstract

Antibody-mediated clearance of hepatitis B surface antigen (HBsAg) from the circulation of chronically infected patients (i.e., seroconversion) is usually associated with increased HBV-specific T cell responsiveness. However, a causative link between serum HBsAg levels and impairment of intrahepatic CD8+ T cells has not been established. Here we addressed this issue by using HBV replication-competent transgenic mice that are depleted of circulating HBsAg, via either spontaneous seroconversion or therapeutic monoclonal antibodies, as recipients of HBV-specific CD8+ T cells. Surprisingly, we found that serum HBsAg clearance has only a minimal effect on the expansion of HBV-specific naive CD8+ T cells undergoing intrahepatic priming. It does not alter their propensity to become dysfunctional, nor does it enhance the capacity of IL-2-based immunotherapeutic strategies to increase their antiviral function. In summary, our results reveal that circulating HBsAg clearance does not improve HBV-specific CD8+ T cell responses in vivo and may have important implications for the treatment of chronic HBV infection.

© 2020 Fumagalli et al.

StephenW

专家杂志

。 2020年11月2日; 217（11）：e20200298。
doi：10.1084 / jem.20200298。
在小鼠HBV感染模型中，血清HBsAg清除率对CD8 + T细胞反应的影响最小
Valeria Fumagalli 1 2，Pietro Di Lucia 1，Valentina Venzin 1 2，Elisa B Bono 1，Robert Jordan 3，Christian R Frey 3，William Delaney 3，Francis V Chisari 4，Luca G Guidotti 1 2，Matteo Iannacone 1 2 5
隶属关系
隶属关系

    1个
    意大利米兰圣拉斐尔科学研究所（IRCCS）圣拉斐尔科学研究所免疫，移植和传染病科。
    2
    维塔礼炮圣拉斐尔大学，意大利米兰。
    3
    吉利德科学公司，福斯特城，CA。
    4
    加利福尼亚州拉霍亚斯克里普斯研究所免疫学和微生物科学系。
    5
    意大利米兰圣拉斐尔科学研究所（IRCS）实验成像中心。

    PMID：32761167 DOI：10.1084 / jem.20200298

抽象

抗体介导的慢性感染患者循环中乙型肝炎表面抗原（HBsAg）清除（即血清转化）通常与HBV特异性T细胞反应性增强有关。但是，血清HBsAg水平与肝内CD8 + T细胞损伤之间的因果关系尚未建立。在这里，我们通过使用具有HBV复制能力的转基因小鼠（通过自发血清转化或治疗性单克隆抗体消耗循环HBsAg）作为HBV特异性CD8 + T细胞的受体，解决了这个问题。令人惊讶地，我们发现血清HBsAg清除率对经历肝内启动的HBV特异性幼稚CD8 + T细胞的扩增仅具有最小的影响。它不会改变其功能障碍的倾向，也不会增强基于IL-2的免疫治疗策略增强其抗病毒功能的能力。总之，我们的结果表明，循环中的HBsAg清除不会改善体内的HBV特异性CD8 + T细胞应答，并且可能对慢性HBV感染的治疗具有重要意义。

©2020 Fumagalli等。

StephenW

https://rupress.org/jem/article- ... 16/jem_20200298.pdf