Brain‐resident memory CD8 + T cells induced by congenital CMV infection prevent brain pathology and virus reactivation

Abstract

<p id="P5">Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with MCMV intraperitoneally is a well-established model of congenital HCMV 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 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. </p>