title: Immune Regulation by T Regulatory Cells in Hepatitis B Virus-Related Inflammation and Cancer.
abstract: Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and hepatitis B virus (HBV) infection is one of the commonest causes in Asian countries. India has the second largest pool after China for hepatitis B-infected subjects. HBV clearance is T cell dependent, and one of the reasons for T cells hyporesponsiveness is due to mass production of regulatory T cells (Tregs) through activation of Notch signalling, which suppress CD4/CD8 T cells. Tregs are important to maintain cellular homoeostasis; however, during viral infection increase of Tregs is inversely proportional to HBV DNA titres. Tregs exert their suppressive effect either via cell-to-cell contact or through release of interleukin (IL)-2, IL-10, TGF-β and IL-35. In Chronic hepatitis B virus CHBV infection, PD-1 pathway also gets activated and is involved in promoting tolerance. However, with Tregs induction, virus-specific T cell responses also get decreased. Circulatory and intratumoural Tregs promote development of HBV-specific HCC more by decreasing and impairing the effector functions of CD8 T cells. Antiviral therapies and PD-1 blockade strategy had shown the inhibition of Tregs and reduction in HBV DNA. However, inhibition of HBV-specific Tregs is major challenge for future therapies. New cytokine blockade therapies have emerged as potential therapeutic potentials.
authors.affiliation: Departments of Molecular and cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Trehanpati
authors.affiliation: Departments of Molecular and cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Vyas
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007194:India; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019562:Viral Load / Q000276:immunology
chemical_list: C508609:IL10 protein, human; C508594:IL2 protein, human; C508586:IL36A protein, human; D007375:Interleukin-1; D007376:Interleukin-2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10