Japan Digestive Disease Week 2021
International Session (Workshop)1 (JSGE, JSH)
November 4, 15:00–17:00, Room 11 (Portopia Hotel South Wing Topaz)
IS-W1-9_H
OX40 stimulation of HBV-specific CD8+ T cells achieves long-term HBs suppression.
- 1
- Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases
- 2
- Department of Virology, Nagoya City University
- 3
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University
AIM: HBs reduction is essential for the functional cure of chronic hepatitis B. Here, we investigated whether HBs can be suppressed by activating HBV-specific CD8+ T cells without reducing the amount of HBV template DNA.
METHODS: Groups of transgenic mice that replicate HBV in the liver (HBV-Tg mice) were adoptively transferred with HBV-specific naive CD8+ T cells. The mice simultaneously received an agonistic OX40 antibody or saline. HBV-specific CD8+ T cell response in the liver was associated with serum HBs antigen and HBs antibody titer over time.
RESULTS: Functionalities of HBV-specific CD8+ T cells were induced on day 3 after OX40 stimulation but rapidly suppressed on day 7. Serum HBs antigens were as high as 343 ± 145 IU/mL before OX40 stimulation, and began to decrease significantly on day 7, and reached as low as 0.1 ± 0.1 IU / mL on day 21. Importantly, even 180 days after OX40 stimulation, serum HBs antigen remained suppressed, although no HBs antibody was detected. Since HBV transgene is integrated into every hepatocyte in HBV transgenic mice, the results suggest that continuous HBs suppression does not require eliminating the template HBV DNA.
CONCLUSION: HBs can be continuously suppressed in the presence of template DNA by transiently stimulating OX40 signaling in HBV-specific CD8+ T cells.
METHODS: Groups of transgenic mice that replicate HBV in the liver (HBV-Tg mice) were adoptively transferred with HBV-specific naive CD8+ T cells. The mice simultaneously received an agonistic OX40 antibody or saline. HBV-specific CD8+ T cell response in the liver was associated with serum HBs antigen and HBs antibody titer over time.
RESULTS: Functionalities of HBV-specific CD8+ T cells were induced on day 3 after OX40 stimulation but rapidly suppressed on day 7. Serum HBs antigens were as high as 343 ± 145 IU/mL before OX40 stimulation, and began to decrease significantly on day 7, and reached as low as 0.1 ± 0.1 IU / mL on day 21. Importantly, even 180 days after OX40 stimulation, serum HBs antigen remained suppressed, although no HBs antibody was detected. Since HBV transgene is integrated into every hepatocyte in HBV transgenic mice, the results suggest that continuous HBs suppression does not require eliminating the template HBV DNA.
CONCLUSION: HBs can be continuously suppressed in the presence of template DNA by transiently stimulating OX40 signaling in HBV-specific CD8+ T cells.
- Index Term 1: OX40
- Index Term 2: CD8+ T cell