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

Or Alfi1, Mevaseret Cohen1, Shikma Bar-On2

  • 1Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.

Cell Reports
|January 24, 2024
PubMed

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 employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal 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 a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.

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