Decidual-tissue resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface

Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employed a unique ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity, recapitulating nonprimary versus primary infection at the authentic maternofetal transmission site. We showed that decidual tissues of women with preconception immunity exhibited intrinsic resistance to HCMV, mounting a rapid activation of tissue resident memory CD8+ and CD4+ T cells upon nonprimary infection. We further revealed the role of HCMV-specific decidual-tissue resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of vaccine against cCMV, and provide insights for further studies of the integrity of immune defense against cCMV and other pathogens in the human maternal-fetal interface.