Unravelling the fate of functional PD1+ T cells in chronic viral hepatitis

Abstract

Hepatitis B virus (HBV) infection can be managed clinically with nucleos(t)ide therapy, which suppresses viral replication; however, these drugs must often be used long term, as they are unable to fully eliminate the virus. For many patients, discontinuation of treatment results in viral resurgence and hepatic flare, and there is not a reliable way to identify those individuals that can be successfully taken off nucleos(t)ide therapy. In this issue of the JCI, Rivino and colleagues report on their use of a multipronged approach to investigate potential biomarkers indicative of HBV-infected patients who can safely stop nucleos(t)ide therapy. The authors identified a population of HBV-specific, PD1-positive T cells that was present in HBV-infected patients who successfully discontinued treatment without hepatic flare, but not in those that developed flare upon treatment cessation. Together, these results support the concept that PD1+ cells may play an important role in viral control, the further evaluation of this T cell subset in preventing hepatic flare, and the development of assays to better detect this PD1+ T cell population in HBV-infected patients on nucleos(t)ide therapy.

Figure 1. A schematic representation of PD1 expression and T cell differentiation in viral hepatitis.

PD1 expression and selected discriminatory markers of T cell differentiation and the generation of T cell memory are shown during clinical stages of infection. These include acute and resolved viral infection (blue lines), chronic infection (red lines), and chronic infection with viral suppression with antiviral therapy (green lines). Partially exhausted T cells with memory potential have been shown to play a role in viral suppression during chronic disease in mouse models and can be expanded after therapy following in vivo or ex vivo antigen rechallenge. Tem, effector memory cells; Tcm, central memory cells; Tpex(M), partially exhausted T cells with memory potential.