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Tytuł:
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Brain-resident memory CD8 T cells induced by congenital CMV infection prevent brain pathology and virus reactivation.
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Autorzy:
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Brizić I; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Šušak B; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Faculty of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina.
Arapović M; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Faculty of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina.
Huszthy PC; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Centre for Immune Regulation, Department of Immunology, University of Oslo, Norway.
Hiršl L; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Kveštak D; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Juranić Lisnić V; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Golemac M; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Pernjak Pugel E; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Tomac J; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Oxenius A; Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
Britt WJ; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Arapović J; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Faculty of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina.
Krmpotić A; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Jonjić S; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
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Źródło:
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European journal of immunology [Eur J Immunol] 2018 Jun; Vol. 48 (6), pp. 950-964. Date of Electronic Publication: 2018 Mar 23.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2005->: Weinheim : Wiley-VCH
Original Publication: Weinheim, Verlag Chemie GmbH.
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MeSH Terms:
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Brain/*immunology
CD8-Positive T-Lymphocytes/*immunology
Cytomegalovirus/*physiology
Cytomegalovirus Infections/*immunology
Muromegalovirus/*physiology
T-Lymphocytes, Cytotoxic/*immunology
Virus Activation/*immunology
Adoptive Transfer ; Animals ; Animals, Newborn ; CD8-Positive T-Lymphocytes/transplantation ; Cells, Cultured ; Congenital Abnormalities ; Disease Models, Animal ; Humans ; Immunologic Memory ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Cytotoxic/transplantation
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Grant Information:
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R01 AI089956 United States AI NIAID NIH HHS
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Contributed Indexing:
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Keywords: Brain pathology; Congenital CMV infection; Microglia; Mouse cytomegalovirus; Tissue-resident memory T cells
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Entry Date(s):
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Date Created: 20180304 Date Completed: 20190128 Latest Revision: 20200225
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Update Code:
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20240104
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PubMed Central ID:
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PMC6422351
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DOI:
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10.1002/eji.201847526
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PMID:
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29500823
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Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8 + T cells in the brain following infection of newborn mice. We show that CD8 + T cells infiltrate the brain and form a pool of tissue-resident memory T cells (T RM cells) that persist for lifetime. Adoptively transferred virus-specific CD8 + T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as T RM cells. Brain CD8 + T RM cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8 + T RM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)