Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models
| Autor: | Yong Lin, Marzena Lenart, Shiou-Hwei Yeh, Michael Roggendorf, Weimin Wu, Mengji Lu, Jieliang Chen, Cong Wang, Zhenghong Yuan, Jia Liu, Ulf Dittmer, Thekla Kemper, Anna D. Kosinska, Zhong Fang, Kirsten K. Dietze, Leila Pishraft-Sabet |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Hepatitis B virus Regulatory T cell Medizin Mice Transgenic medicine.disease_cause T-Lymphocytes Regulatory Virus Statistics Nonparametric 03 medical and health sciences Mice Random Allocation Immune system Sex Factors Risk Factors medicine Animals Hepatitis B Vaccines Lymphocyte Count Cells Cultured Hepatitis Analysis of Variance Immunity Cellular Hepatology biology Woodchuck hepatitis virus Vaccination biology.organism_classification medicine.disease Hepatitis B Virology digestive system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Viral replication Immunology Female CD8 |
| Zdroj: | Hepatology (Baltimore, Md.). 66(1) |
| ISSN: | 1527-3350 |
| Popis: | Hepatitis B virus (HBV) infection shows significant gender-related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. The gender-associated differences in HBV replication and viral protein levels may be associated with distinct HBV-specific immune responses in the host. In the present study, we examined the impact of gender on HBV-specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydrodynamic injection with the HBV genome mimicked acute HBV infection, whereas the efficacy of therapeutic vaccination was studied in the woodchuck hepatitis virus transgenic mouse model. Consistent with previous reports, significantly higher HBV DNA and protein levels were detected in male compared to female mice. Although hydrodynamic injection with the HBV genome resulted in similar numbers of intrahepatic HBV-specific cluster of differentiation 8-positive (CD8+ ) T cells, their functionality was significantly reduced in males and correlated with higher numbers of intrahepatic regulatory T cells (Tregs). Similar effects were observed in woodchuck hepatitis virus transgenic mice immunized with a DNA prime-recombinant adenovirus boost vaccination protocol. Male mice showed functionally suppressed woodchuck hepatitis virus-specific CD8+ T-cell responses in the liver and significantly higher numbers of intrahepatic Tregs compared to females. Blockade of Treg responses in male mice led to augmented effector functions of specific CD8+ T cells and subsequently improved virus control in both models of transient and persistent hepadnaviral infection. Conclusion The functionality of virus-specific CD8+ T cells in male mice was suppressed by intrahepatic Tregs and inversely correlated with levels of hepadnaviral DNA and viral protein; the induction of intrahepatic Tregs by viral replication and/or protein levels may explain the gender-related differences in the outcomes of HBV infection and limit the success of immunotherapeutic strategies in male patients. (Hepatology 2017;66:69-83). |
| Databáze: | OpenAIRE |
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