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Immune Memory and Exhaustion: Clinically Relevant Lessons from the LCMV Model

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Crossroads Between Innate and Adaptive Immunity V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 850))

Abstract

The development of dysfunctional or exhausted T cells is characteristic of immune responses to chronic viral infections and cancer. Exhausted T cells are defined by reduced effector function, sustained upregulation of multiple inhibitory receptors, an altered transcriptional program and perturbations of normal memory development and homeostasis. This review focuses on (a) illustrating milestone discoveries that led to our present understanding of T cell exhaustion, (b) summarizing recent developments in the field, and (c) identifying new challenges for translational research. Exhausted T cells are now recognized as key therapeutic targets in human infections and cancer. Much of our knowledge of the clinically relevant process of exhaustion derives from studies in the mouse model of Lymphocytic choriomeningitis virus (LCMV) infection. Studies using this model have formed the foundation for our understanding of human T cell memory and exhaustion. We will use this example to discuss recent advances in our understanding of T cell exhaustion and illustrate the value of integrated mouse and human studies and will emphasize the benefits of bi-directional mouse-to-human and human-to-mouse research approaches.

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Authors and Affiliations

  1. Division of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland

    D. Zehn

  2. Department of Microbiology, Institute for Immunology, Philadelphia, PA, USA

    E. J. Wherry

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  1. D. Zehn
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  2. E. J. Wherry
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Correspondence to D. Zehn .

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Editors and Affiliations

  1. Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immun, La Jolla, USA

    Stephen P. Schoenberger

  2. Department Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Peter D. Katsikis

  3. Yerkes National Primate Research Center, Emory University Emory Vaccine Center &, Atlanta, Georgia, USA

    Bali Pulendran

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Zehn, D., Wherry, E. (2015). Immune Memory and Exhaustion: Clinically Relevant Lessons from the LCMV Model. In: Schoenberger, S., Katsikis, P., Pulendran, B. (eds) Crossroads Between Innate and Adaptive Immunity V. Advances in Experimental Medicine and Biology, vol 850. Springer, Cham. https://doi.org/10.1007/978-3-319-15774-0_10

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