Nature Immunology, Published online: 08 July 2025; doi:10.1038/s41590-025-02204-9

Effector CD4⁺ T cells restore antiviral CD8⁺ T cell function in the liver by licensing Kupffer cells via CD40–CD40L interactions. This triggers IL-27 production and reprograms the hepatic immune environment. This liver-intrinsic pathway of T cell help is relevant for chronic hepatitis B virus infection and may apply to other conditions with persistent antigen stimulation, such as cancer.



Summary

A new study in Nature Immunology reveals that effector CD4⁺ T cells restore antiviral CD8⁺ T cell function in the liver during chronic infection. This process involves CD40–CD40L interactions that license Kupffer cells, leading to IL-27 production and reprogramming the liver’s immune environment. This CD4⁺ T cell-mediated "help" within the liver is crucial for fighting persistent viral infections, specifically chronic hepatitis B virus (HBV). The research suggests this mechanism, driven by continuous antigen stimulation, might also be relevant in other disease contexts like cancer, where immune responses are dysregulated.

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