Tissue-Resident CD8+ T Cells as Mediators of Protective Immunity in Breast Milk Transmission of Human Cytomegalovirus

Abstract

While the role of breast milk antibodies to protect infants from human cytomegalovirus (HCMV) has been investigated, the role of T-cells has received little attention. We compared the frequency of memory T-cell populations in breast milk between mothers of infants who acquired breast milk HCMV (transmitters) and those with uninfected infants (nontransmitters). Nontransmitter mothers had an increased frequency of CD8+ effector memory T-cells (Tem) in their breast milk. In addition, we describe tissue-resident memory T cells (Trm) in breast milk and demonstrate most were Tem. We present data that nontransmitter mothers have increased frequency of CD8+ Trm in their breast milk when compared to transmitters and that Trm frequency is inversely correlated with breast milk HCMV viral load. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in nontransmitters and demonstrate that these cells comprise CD8+ Trm. These studies suggest that CD8+ Trm may play a role in preventing viral transmission via breast milk to infants.

Keywords: CMV; T cells; breast milk; tissue-resident T cells.