Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection.
Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection.
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DOI：
10.1084/jem.20200298
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发表时间：
2020-11-02
期刊：
影响因子：
--
通讯作者：
Iannacone M
中科院分区：
文献类型：
--
作者：
Fumagalli V;Di Lucia P;Venzin V;Bono EB;Jordan R;Frey CR;Delaney W;Chisari FV;Guidotti LG;Iannacone M
抗体介导的循环HBsAg的清除对经历肝内引发的HBV特异性CD 8 + T细胞的扩增具有最小的影响。它不会改变它们分化为功能失调的细胞，也不会通过免疫策略增强它们的功能恢复。抗体介导的从慢性感染患者的循环中清除B型肝炎表面抗原（HBsAg）（即，血清转化）通常与HBV特异性T细胞反应性增加有关。然而，血清HBsAg水平和肝内CD 8 + T细胞损伤之间的因果关系尚未建立。在这里，我们解决了这个问题，通过使用HBV复制能力转基因小鼠，通过自发血清转换或治疗性单克隆抗体，作为HBV特异性CD 8 + T细胞的受体，循环HBsAg耗尽。令人惊讶的是，我们发现血清HBsAg清除对经历肝内引发的HBV特异性初始CD 8 + T细胞的扩增只有最小的影响。它不会改变它们变得功能障碍的倾向，也不会增强基于IL-2的免疫策略的能力以增加它们的抗病毒功能。总之，我们的研究结果表明，循环HBsAg清除不会改善体内HBV特异性CD 8 + T细胞应答，可能对慢性HBV感染的治疗具有重要意义。
Antibody-mediated clearance of circulating HBsAg has minimal impact on the expansion of HBV-specific CD8+ T cells undergoing intrahepatic priming. It does not alter their differentiation into dysfunctional cells, nor does it enhance their functional restoration by immunotherapeutic strategies. 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.
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DOI：
10.4049/jimmunol.1502061
发表时间：
2016-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhu D;Liu L;Yang D;Fu S;Bian Y;Sun Z;He J;Su L;Zhang L;Peng H;Fu YX
通讯作者：
Fu YX
影响因子：
3.7
作者：
Seeger, Christoph;Mason, William S.
通讯作者：
Mason, William S.
影响因子：
5.4
作者：
GUIDOTTI, LG;MATZKE, B;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
15.9
作者：
KIM, CY;TILLES, JG
通讯作者：
TILLES, JG
影响因子：
15.9
作者：
Manjunath, N;Shankar, P;von Andrian, UH
通讯作者：
von Andrian, UH