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Immune Regulation by T Regulatory Cells in Hepatitis B Virus‐Related Inflammation and Cancer
Author(s) -
Trehanpati N.,
Vyas A. K.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12524
Subject(s) - hepatitis b virus , immunology , immune system , cd8 , immunotherapy , medicine , inflammation , t cell , blockade , liver cancer , hepatitis b , hepatocellular carcinoma , virus , cancer research , receptor
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 CD 4/ CD 8 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 CD 8 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.