Modulation of regulatory T-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis B

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Itziar OtanoGloria González-Aseguinolaza

Abstract

Regulatory T cells (Treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. Woodchucks (Marmota monax) infected with the woodchuck hepatitis virus (WHV) represent the best animal model for chronic hepatitis B virus (HBV) infection. Examination of intrahepatic and peripheral Treg in uninfected and WHV chronically infected woodchucks showed a significant increase of intrahepatic Treg numbers in chronically infected animals, whereas no differences were found in peripheral blood. In agreement with these data, higher expression levels of Forkhead box P3 (Foxp3), interleukin (IL)-10, transforming growth factor beta (TGF-β) were detected in the liver of chronic WHV carriers in comparison to uninfected animals. Furthermore, treatment of WHV-infected animals with an adenovirus encoding IL-12 failed to reduce viral load, a finding that was associated with lymphocyte unresponsiveness to IL-12 stimulation in vitro. We observed that TGF-β and Treg play a major role in the lack of lymphocyte response to IL-12 stimulation, as TGF-β inhibition and Treg depletion allowed recovery of T-cell responsiveness to this cytokine. Based on these results, woodchucks were treated with IL-12 in combina...Continue Reading

References

Feb 23, 1999·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·C FerrariF Fiaccadori
May 8, 2002·The Journal of Experimental Medicine·Stephanie ReignatAntonio Bertoletti
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Namita MisraSrini V Kaveri
Mar 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jeroen N StoopHarry L A Janssen
Oct 27, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eirini I RigopoulouNikolai V Naoumov
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dongping XuFu-Sheng Wang
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holly MaierFrancis V Chisari
Oct 20, 2007·Nature Reviews. Immunology·Yasmine Belkaid
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucía Gil-GuerreroJuan José Lasarte
Aug 13, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexander EvansNikolai V Naoumov
Jan 1, 2009·Journal of Virology·Julien CrettazGloria Gonzalez-Aseguinolaza
Apr 29, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Brian J McMahon
Aug 29, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna S F Lok, Brian J McMahon
Jul 28, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Ji ChenGui-Qiang Wang
Aug 4, 2010·Anti-cancer Drugs·Miao YuJinshan Zhang
Nov 10, 2010·Antiviral Therapy·Antonio BertolettiCarlo Ferrari
Mar 2, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna SchurichMala K Maini
Apr 29, 2011·BMB Reports·Hyun-Tak JinSang-Jun Ha

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Citations

Aug 18, 2012·Seminars in Immunopathology·Maura DandriJörg Petersen
Oct 14, 2014·Future Virology·Rama Kapoor, Shyam Kottilil
Mar 13, 2014·BMC Systems Biology·Geoffroy AndrieuxNathalie Théret
Apr 19, 2013·Expert Opinion on Investigational Drugs·Ruben Hernandez-AlcocebaJesus Prieto
Dec 19, 2019··Tri Nugraha SusilawatiAlfin Titian Permata

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