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Medical Microbiology and Immunology

, Volume 208, Issue 3–4, pp 487–494 | Cite as

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

  • Ilija Brizić
  • Lea Hiršl
  • Marko Šustić
  • Mijo Golemac
  • William J. Britt
  • Astrid Krmpotić
  • Stipan JonjićEmail author
Original Investigation
  • 298 Downloads
Part of the following topical collections:
  1. The Special Issue on Immunological Imprinting during Chronic Viral Infection

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.

Keywords

Mouse cytomegalovirus Tissue-resident memory T cells Brain pathology CD4 T cells Congenital CMV infection 

Notes

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.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ilija Brizić
    • 1
    • 2
  • Lea Hiršl
    • 1
    • 2
  • Marko Šustić
    • 1
  • Mijo Golemac
    • 1
  • William J. Britt
    • 3
  • Astrid Krmpotić
    • 1
  • Stipan Jonjić
    • 1
    • 2
    Email author
  1. 1.Department of Histology and Embryology, Faculty of MedicineUniversity of RijekaRijekaCroatia
  2. 2.Center for Proteomics, Faculty of MedicineUniversity of RijekaRijekaCroatia
  3. 3.Department of MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA

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