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CD4 T cells are required for maintenance of CD8 TRM cells and virus control in the brain of MCMV-infected newborn mice

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Abstract

Cytomegalovirus (CMV) infection is a significant public health problem. Congenital CMV infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and sensorineural hearing loss. Immune protection against mouse cytomegalovirus (MCMV) is primarily mediated by NK cells and CD8+ T cells, while CD4+ T cells are not needed for control of MCMV in majority of organs in immunocompetent adult mice. Here, we set out to determine the role of CD4+ T cells upon MCMV infection of newborn mice. We provide evidence that CD4+ T cells are essential for clearance of MCMV infection in brain of neonatal mice and for prevention of recurrence of latent MCMV. In addition, we provide evidence that CD4+ T cells are required for induction and maintenance of tissue-resident memory CD8+ T cells in the brain of mice perinatally infected with MCMV.

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Acknowledgements

We thank Edvard Ražić, Dijana Rumora, Miro Samsa, Edvard Marinović, Ante Miše and Tina Rudančić for the excellent technical support. The study was supported by NIH (1RO1AI089956-01A1) (to W.J.B. and S.J.), by the European Regional Development Fund (KK.01.1.1.01.0006) (to S.J.) and University of Rijeka (uniri-biomed-18-297 to I.B.).

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  1. Ilija Brizić and Lea Hiršl have contributed equally.

Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000, Rijeka, Croatia

    Ilija Brizić, Lea Hiršl, Marko Šustić, Mijo Golemac, Astrid Krmpotić & Stipan Jonjić

  2. Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

    Ilija Brizić, Lea Hiršl & Stipan Jonjić

  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA

    William J. Britt

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  1. Ilija Brizić
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This article is part of the Special Issue on Immunological Imprinting during Chronic Viral Infection.

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Brizić, I., Hiršl, L., Šustić, M. et al. CD4 T cells are required for maintenance of CD8 TRM cells and virus control in the brain of MCMV-infected newborn mice. Med Microbiol Immunol 208, 487–494 (2019). https://doi.org/10.1007/s00430-019-00601-0

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