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World J Gastroenterol. Mar 28, 2013; 19(12): 1877-1889
Published online Mar 28, 2013. doi: 10.3748/wjg.v19.i12.1877
Role of T cell death in maintaining immune tolerance during persistent viral hepatitis
Juan Ramón Larrubia, Megha Uttam Lokhande, Silvia García-Garzón, Joaquín Miquel, Dolores Subirá, Eduardo Sanz-de-Villalobos
Juan Ramón Larrubia, Megha Uttam Lokhande, Silvia García-Garzón, Joaquín Miquel, Dolores Subirá, Eduardo Sanz-de-Villalobos, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, 19002 Guadalajara, Spain
Author contributions: Larrubia JR and Lokhande MU contributed equally towards the conception and design of the review; Larrubia JR and Lokhande MU co-wrote and Larrubia JR revised the manuscript; García-Garzón S, Miquel J, Subirá D and Sanz-de-Villalobos E contributed equally to the supportive work and supervision.
Supported by Grants from “Fiscam” JCCM, Ayuda para proyectos de investigación en salud, PI-2010/022; “Fundación de Investigación Médica Mutua Madrileña”, Beca Ayudas a la Investigación FMMM, 8922/2011 and A research grant from “Asociación de Hepatología Translacional”, No. AHT 2010-01, to Lokhande MU
Correspondence to: Megha Uttam Lokhande, MSc, Translational Hepatology Unit. Guadalajara University Hospital. University of Alcalá. Donante de Sangre st., 19002 Guadalajara, Spain.
Telephone: +34-949-209200 Fax: +34-949-209259
Received: September 14, 2012
Revised: December 20, 2012
Accepted: December 25, 2012
Published online: March 28, 2013

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