Kinetics analysis of the function of splenocytes from acuteresolving HBV-mice in breaking HBV tolerance
详细信息    查看官网全文
摘要
Background: Effective adaptive immune responses are vital for the clearance of HBV infection. However, little is known about how the antiviral function of different immune cells of peripheral lymphoid organs changes during the course of acute-resolving HBV infection. Here, we investigated the kinetics of functional change of different splenocytes from acute-resolving HBV-mice in breaking HBV tolerance using HBV hydrodynamic injection(HI) mouse model.Methods: HI was performed to establish acute-resolving( p SM2 plasmid) or persisting(p AAV/HBV1.2 plasmid) HBV replication in CD45.1 and CD45.2 C57BL/6 mice. Total splenocytes, splenic CD8+ T cells and splenocytes without CD8+ T cells(non-CD8) were purified from HBV acute-resolving mice at different time points post virus exposure and were adoptively transferred to HBV persistence mice. The viremia in the recipient mice was monitored. The phenotype and function of donor immune cells were analyzed by flow cytometry.Results: Viral clearance was achieved in HBV persistence mice by adoptive transfer of 14dpi(days post injection) total splenocytes and 21 dpi purified splenic CD8+ T cells from acute-resolving HBV-mice. Besides, adoptive transfer of 7dpi non-CD8, 14 dpi CD8+ T cells and non-CD8, 21 dpi total splenocytes, and 28 dpi non-CD8 led to a better control of viral replication. Interestingly, adoptive transfer of 21 dpi non-CD8 and 28 dpi CD8+ T cells resulted in a delayed HBV clearance. We observed increased CD8+ T cell infiltration in the liver in 14 dpi total splenocytes and 21 dpi CD8+ T cell transferred group. These CD8+ T cells showed an activation phenotype and increased IFN-γ production compared to that in other cells transferred groups.Conclusions: The antiviral function varies in different splenocytes as well as at different time points during the course of acute-resolving HBV replication. The achievement of breaking HBV tolerance relies on the activation of both splenic CD8+ T cells and non-CD8 cells. The activation of non-CD8 splenocytes seems to happen prior to the activation of CD8+ T cells post virus exposure. The non-CD8 also showed a negative immune regulation property during the late phase of HBV clearance.
Background: Effective adaptive immune responses are vital for the clearance of HBV infection. However, little is known about how the antiviral function of different immune cells of peripheral lymphoid organs changes during the course of acute-resolving HBV infection. Here, we investigated the kinetics of functional change of different splenocytes from acute-resolving HBV-mice in breaking HBV tolerance using HBV hydrodynamic injection(HI) mouse model.Methods: HI was performed to establish acute-resolving( p SM2 plasmid) or persisting(p AAV/HBV1.2 plasmid) HBV replication in CD45.1 and CD45.2 C57BL/6 mice. Total splenocytes, splenic CD8+ T cells and splenocytes without CD8+ T cells(non-CD8) were purified from HBV acute-resolving mice at different time points post virus exposure and were adoptively transferred to HBV persistence mice. The viremia in the recipient mice was monitored. The phenotype and function of donor immune cells were analyzed by flow cytometry.Results: Viral clearance was achieved in HBV persistence mice by adoptive transfer of 14dpi(days post injection) total splenocytes and 21 dpi purified splenic CD8+ T cells from acute-resolving HBV-mice. Besides, adoptive transfer of 7dpi non-CD8, 14 dpi CD8+ T cells and non-CD8, 21 dpi total splenocytes, and 28 dpi non-CD8 led to a better control of viral replication. Interestingly, adoptive transfer of 21 dpi non-CD8 and 28 dpi CD8+ T cells resulted in a delayed HBV clearance. We observed increased CD8+ T cell infiltration in the liver in 14 dpi total splenocytes and 21 dpi CD8+ T cell transferred group. These CD8+ T cells showed an activation phenotype and increased IFN-γ production compared to that in other cells transferred groups.Conclusions: The antiviral function varies in different splenocytes as well as at different time points during the course of acute-resolving HBV replication. The achievement of breaking HBV tolerance relies on the activation of both splenic CD8+ T cells and non-CD8 cells. The activation of non-CD8 splenocytes seems to happen prior to the activation of CD8+ T cells post virus exposure. The non-CD8 also showed a negative immune regulation property during the late phase of HBV clearance.
引文

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700