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

Area of Science:

• Immunology
• Neuroscience
• Virology

Background:

• Congenital human cytomegalovirus (HCMV) infection is a primary cause of lifelong neurodevelopmental deficits.
• The mouse cytomegalovirus (MCMV) model in newborn mice accurately mimics congenital HCMV infection, including brain pathology via hematogenous spread.

Purpose of the Study:

• To investigate the role, dynamics, and phenotype of CD8+ T cells in the brain during MCMV infection in newborn mice.
• To determine if adoptively transferred virus-specific CD8+ T cells can confer protection and establish long-term brain immunity.

Main Methods:

• Utilized a well-established mouse model of congenital MCMV infection.
• Investigated the infiltration, persistence, and function of CD8+ T cells in the brain.
• Employed adoptive transfer of virus-specific CD8+ T cells to assess protective immunity.

Main Results:

• CD8+ T cells were found to infiltrate the brain and establish a persistent pool of tissue-resident memory T (T_RM) cells.
• Adoptive transfer of virus-specific CD8+ T cells protected newborn mice against MCMV, reduced brain pathology, and resulted in long-term brain T_RM cell presence.
• Brain CD8+ T_RM cells demonstrated longevity, slow proliferation, responsiveness to local challenge, and control of latent MCMV, with depletion leading to reactivation and inflammation.

Conclusions:

• CD8+ T cells establish a long-lived, protective memory population within the brain following congenital MCMV infection.
• Brain-resident CD8+ T_RM cells are crucial for controlling latent MCMV and preventing neuroinflammation, highlighting their therapeutic potential.