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      To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections

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          Abstract

          CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bT RM). CD8 bT RM are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bT RM have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bT RM and discuss their roles in controlling viral infections of the brain.

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          Most cited references57

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          Microglia development and function.

          Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques.
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            Effector and memory CTL differentiation.

            Technological advances in recent years have allowed for an ever-expanding ability to analyze and quantify in vivo immune responses. MHC tetramers, intracellular cytokine staining, an increasing repertoire of transgenic and "knockout" mice, and the detailed characterization of a variety of infectious models have all facilitated more precise and definitive analyses of the generation and function of cytotoxic T lymphocytes (CTL). Understanding the mechanisms behind the differentiation of effector and memory CTL is of increasing importance to develop vaccination strategies against a variety of established and emerging infectious diseases. This review focuses on recent advances in our understanding of how effector and memory CTL differentiate and survive in vivo in response to viral or bacterial infection.
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              Understanding Subset Diversity in T Cell Memory.

              Considerable advances have been made in recent years in understanding the generation and function of memory T cells. Memory T cells are typically parsed into discreet subsets based on phenotypic definitions that connote distinct roles in immunity. Here we consider new developments in the field and focus on how emerging differences between memory cells with respect to their trafficking, metabolism, epigenetic regulation, and longevity may fail to fit into small groups of "memory subsets." Rather, the properties of individual memory T cells fall on a continuum within each of these and other parameters. We discuss how this continuum influences the way that the efficacy of vaccination is assessed, as well as the suitability of a memory population for protective immunity.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                11 September 2019
                September 2019
                : 11
                : 9
                : 842
                Affiliations
                [1 ]Department of Neurology, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
                [2 ]Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
                [3 ]Biocon Bristol-Myers Squib Research and Development Center, Biocon Park, Bengaluru 560099, India
                Author notes
                Author information
                https://orcid.org/0000-0002-7969-2841
                Article
                viruses-11-00842
                10.3390/v11090842
                6784233
                31514273
                db4dc0c9-b146-4c98-a9da-fadccbf2da37
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 July 2019
                : 06 September 2019
                Categories
                Review

                Microbiology & Virology
                cd8 t cells,resident memory t cells,viral infection,central nervous system

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