Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number20200298
JournalJournal of Experimental Medicine
Volume217
Issue number11
DOIs
Publication statusPublished - Aug 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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