Therapeutic potential of co-signaling receptor modulation in hepatitis B.

ABSTRACT: Reversing CD8⁺ T cell dysfunction is crucial in treating chronic hepatitis B virus (HBV) infection, yet specific molecular targets remain unclear. Our study analyzed co-signaling receptors during hepatocellular priming and traced the trajectory and fate of dysfunctional HBV-specific CD8⁺ T cells. Early on, these cells upregulate PD-1, CTLA-4, LAG-3, OX40, 4-1BB, and ICOS. While blocking co-inhibitory receptors had minimal effect, activating 4-1BB and OX40 converted them into antiviral effectors. Prolonged stimulation led to a self-renewing, long-lived, heterogeneous population with a unique transcriptional profile. This includes dysfunctional progenitor/stem-like (T_SL) cells and two distinct dysfunctional tissue-resident memory (T_RM) populations.

SUBMITTER: Andreata F 

PROVIDER: S-EPMC11290321 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature