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. 2019 Aug;208(3-4):487-494. doi: 10.1007/s00430-019-00601-0. Epub 2019 Mar 28.

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / immunology*
  • Brain / virology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus Infections / immunology*
  • Disease Models, Animal
  • Mice
  • Muromegalovirus / growth & development*
  • Muromegalovirus / immunology*