Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection
Authors: Valeria Fumagalli, Pietro Di Lucia, Valentina Venzin, Elisa B. Bono, Robert Jordan, Christian R. Frey, William Delaney, Francis V. Chisari, Luca G. Guidotti, Matteo Iannacone
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.
Reference: Valeria Fumagalli, Pietro Di Lucia, Valentina Venzin, Elisa B. Bono, Robert Jordan, Christian R. Frey, William Delaney, Francis V. Chisari, Luca G. Guidotti, Matteo Iannacone; Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection. J Exp Med 2 November 2020; 217 (11): e20200298. doi: https://doi.org/10.1084/jem.20200298
The authors used Bio X Cell's InVivoMAb anti-mouse IL-2 (Clone S4B6-1) in this research study.