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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
[Antiviral effect of human CTLs activated by HBsAg stimulated dendritic cells in vitro]
Li-he Xing1, Fu-sheng Wang, Chuan-lin Zhu
1Institute of Infectious Diseases, The No.302 Hospital of PLA, Beijing, 100039, China.
Insights
Human dendritic cells (DCs) stimulated with Hepatitis B surface antigen (HBsAg) effectively induce T lymphocytes. These activated DCs and resulting T cells specifically inhibit Hepatitis B e-antigen (HBeAg) expression in cell cultures.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Context:
- Chronic Hepatitis B virus (HBV) infection remains a significant global health challenge.
- Current treatments have limitations, necessitating novel therapeutic strategies.
- Dendritic cells (DCs) are potent antigen-presenting cells crucial for initiating adaptive immune responses.
Purpose:
- To evaluate the capacity of human dendritic cells (DCs) to induce a specific T lymphocyte response.
- To assess the effect of HBsAg-stimulated DCs on Hepatitis B e-antigen (HBeAg) and Hepatitis B surface antigen (HBsAg) expression in vitro.
- To explore the potential of DC-based immunotherapy for chronic HBV infection.
Summary:
- Human DCs were generated and pulsed with purified HBsAg, then co-cultured with autologous T lymphocytes.
- DC stimulation enhanced T lymphocyte proliferation and the generation of cytotoxic T lymphocytes (CTLs).
- HBsAg-pulsed DCs successfully stimulated specific CTLs that significantly inhibited HBeAg expression in 2.2.15 cell culture supernatant, but not HBsAg expression.
Impact:
- Demonstrates that HBsAg-stimulated DCs can generate antigen-specific CTLs capable of suppressing a key viral antigen (HBeAg).
- Highlights the potential of DC-based vaccines as a future antiviral therapy for chronic Hepatitis B.
- Provides a foundation for further research into DC immunotherapy for viral infections.
Objective:
To investigate the ability of human dendritic cells (DCs) inducing specific T lymphocyte response and inhibit the expression of HBeAg and HBsAg in 2.2.15 cell culture supernatant.
Methods:
DCs were prepared from peripheral blood mononuclear cells induced with granulocyte macrophage colony-stimulating factor(GM-CSF) and interleukin 4. DCs was impulsed with pure HBsAg before DCs maturation and cocultured with self-blood T lymphocyte, while DCs without pure HBsAg stimulated group, T lymphocyte group and only T lymphocyte group were prepared as control group. The culture supernatant of 2.2.15 cell with stimulated T lymphocytes was collected on day 1, day 3, day 5 and day 7, respectively. The expressed levels of HBeAg and HBsAg were detected by ELISA method.
Results:
DCs after antigen stimulation had a strong ability to present antigen and induce immune activation, DCs after loading with antigen in normal control and chronic hepatitis patients group had stronger stimulative ability for T lymphocytes proliferation than that of DCs without loading with antigen and only T lymphocyte group(P less than 0.01). The stimulating ability of DCs had a positive correlation to the dosage of loaded antigen; CTLs produced as a result of DCs stimulation had a specific inhibitive effect on the expression of HBeAg in 2.2.15 cell supernatant,but not on the expression of HbsAg.
Conclusion:
Human dendritic cells stimulated with HBsAg in vitro can efficiently present antigen and stimulate the production of specific CTLs to HBV, which can efficiently inhibit the expression of HBeAg in 2.2.15 cell supernatant- DC vaccine may become an antiviral therapy strategy for chronic hepatitis B virus infected patients in future.
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