The Importance of HBV-Specific CD8⁺ T Cells and Their Antiviral Efficacy

CD8⁺ T cells play a crucial role in controlling the hepatitis B virus (HBV) infection. This is important because HBV can cause chronic liver disease and even progress to hepatocellular carcinoma (HCC). However, studying the mechanisms of how these T cells work against HBV has been hampered by limitations in model systems.

In my MD thesis, I developed a new cell culture model using HepG2hNTCP cells infected with HBV. These cells can process viral antigens and present them to HBV-specific CD8⁺ T cells. This model allows for a more detailed analysis of how these T cells work against the virus. Here are the key findings:

• The HBV-infected HepG2hNTCP cells effectively induced the typical functions of CD8⁺ T cells. These functions include the production of interferon-gamma (IFN-γ) and tumor necrosis factor (TNF), as well as degranulation.
• We found that HBV-specific CD8⁺ T cells significantly reduced the amount of virus in infected cells. This highlights the effectiveness of these T cells in controlling HBV infection.
• The study showed that both cytolytic (cell-killing) and non-cytolytic mechanisms were involved in the antiviral activity of CD8⁺ T cells. While direct contact with infected cells led to a greater reduction in viral load, a significant reduction was also observed when the T cells were separated from infected cells by a membrane. This suggests that T cells can control HBV infection through both direct killing of infected cells and the release of soluble factors.

We created a novel model to study the antiviral effects of HBV-specific CD8⁺ T cells. This model could be a valuable tool for future research aimed at understanding and improving immune responses against HBV.