Role of T cell death in maintaining immune tolerance during persistent viral hepatitis

World J Gastroenterol. 2013 Mar 28;19(12):1877-89. doi: 10.3748/wjg.v19.i12.1877.

Abstract

Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate naïve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.

Keywords: Apoptosis; Apoptotic pathways; Bcl-2 interacting mediator; Hepatitis C virus immune tolerance; Liver tolerance; Specific cytotoxic T lymphocytes; T cell death; Viral hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / physiology
  • Bcl-2-Like Protein 11
  • Cell Death / immunology
  • Hepatitis, Viral, Human / immunology*
  • Hepatitis, Viral, Human / metabolism
  • Humans
  • Immune Tolerance*
  • Liver / immunology
  • Liver / pathology
  • Membrane Proteins / physiology
  • Proto-Oncogene Proteins / physiology
  • T-Lymphocytes / pathology*

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Membrane Proteins
  • Proto-Oncogene Proteins