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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

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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Correspondence to Stipan Jonjić.

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

Edited by: Matthias J. Reddehase.

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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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Keywords

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