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Viruses 2019, 11(2), 156; https://doi.org/10.3390/v11020156

Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Received: 15 January 2019 / Revised: 8 February 2019 / Accepted: 9 February 2019 / Published: 13 February 2019
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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Abstract

Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental for identifying T cell exhaustion and this system has been invaluable for uncovering the complexity, regulators, and consequences of this state. These findings have been directly relevant for understanding why ineffective T cell responses commonly arise during many chronic infections including HIV and HCV, as well as during tumor outgrowth. The principal feature of exhausted T cells is the inability to elaborate the array of effector functions necessary to contain the underlying infection or tumor. Using LCMV to determine how to prevent and reverse T cell exhaustion has highlighted the potential of checkpoint blockade therapies, most notably PD-1 inhibition strategies, for improving cellular immunity under conditions of antigen persistence. Here, we discuss the discovery, properties, and regulators of exhausted T cells and highlight how LCMV has been at the forefront of advancing our understanding of these ineffective responses. View Full-Text
Keywords: LCMV; immune exhaustion; T cells; checkpoint inhibitors; chronic infection; antiviral responses LCMV; immune exhaustion; T cells; checkpoint inhibitors; chronic infection; antiviral responses
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Kahan, S.M.; Zajac, A.J. Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus. Viruses 2019, 11, 156.

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