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

• Published in: World journal of gastroenterology : WJG Vol. 19; no. 12; pp. 1877 - 1889
• Main Authors: Larrubia, Juan Ramón, Lokhande, Megha Uttam, García-Garzón, Silvia, Miquel, Joaquín, Subirá, Dolores, Sanz-de-Villalobos, Eduardo
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 28-03-2013
• Subjects: 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; Review; T-Lymphocytes - pathology; Specific cytotoxic T lymphocytes; T cell death; Viral hepatitis; Bcl-2 interacting mediator; Hepatitis C virus immune tolerance; Apoptotic pathways; Liver tolerance; Apoptosis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v19.i12.1877

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.