CD4⁺ T cells license Kupffer cells to reverse CD8⁺ T cell dysfunction induced by hepatocellular priming.

ABSTRACT: Chronic hepatitis B virus (HBV) infection is marked by dysfunctional HBV-specific CD8⁺ T cells, and restoring their effector activity is a major therapeutic goal. Here, we generated HBV-specific CD4⁺ T cell receptor transgenic mice to show that CD4⁺ effector T cells can prevent and reverse the CD8⁺ T cell dysfunction induced by hepatocellular priming. This rescue enhances antiviral CD8⁺ T cell function and suppresses viral replication. CD4⁺ T cell help occurs directly within the liver, independent of secondary lymphoid organs, and requires local antigen recognition. Kupffer cells, rather than dendritic cells, are the critical antigen-presenting platform. CD4⁺ T cells license Kupffer cells via CD40-CD40L interactions, trigger

SUBMITTER: Venzin V 

PROVIDER: S-EPMC12307227 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature