title: Role of T cell death in maintaining immune tolerance during persistent viral hepatitis.
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.
authors.affiliation: Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, 19002 Guadalajara, Spain.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Larrubia
authors.forename: Megha Uttam
authors.initials: MU
authors.lastname: Lokhande
authors.forename: Silvia
authors.initials: S
authors.lastname: García-Garzón
authors.forename: Joaquín
authors.initials: J
authors.lastname: Miquel
authors.forename: Dolores
authors.initials: D
authors.lastname: Subirá
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sanz-de-Villalobos
mesh_terms: D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000276:immunology; D006525:Hepatitis, Viral, Human / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D008099:Liver / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins
keywords: Apoptosis; Apoptotic pathways; Bcl-2 interacting mediator; Hepatitis C virus immune tolerance; Liver tolerance; Specific cytotoxic T lymphocytes; T cell death; Viral hepatitis