Frontline Science: Breast milk confers passive cellular immunity via CD8-dependent mechanisms

Most modern research into the immune effects of breast milk has focused on the impacts of immunoglobulin or oligosaccharide content. However, immediately prior to parturition, the cell populations of breast milk become selectively enriched for CD8+ T cells of an effector memory subtype. Despite this observation that the cellular content of breast milk contains a distinct leukocyte population when compared to peripheral blood, the physiologic role of these CD8+ effector memory cells is unknown. Research encompassing animal models and humans has demonstrated that leukocytes are capable of transferring antigen-specific immunity even when lysed, dialyzed to enrich for fractions less than 10 kDa, and orally administered. Our previous work built upon these reports to elucidate several aspects of this dialyzable leukocyte extract (DLE) activity: only DLE from T effector memory CD8+ cells was capable of transferring antigen-specific immunity; the DLE activity was TCRβ dependent; dendritic cells (DCs) were the cellular target of DLE; and DLE enhanced immune activity in epithelial challenge models via induction of IL-6 from DCs. Herein, we reveal that breast milk dialysate activates similar cytokine and genetic pathways as DLE taken from peripheral blood and murine spleens through TCRβ- and CD8-dependent mechanisms. These findings suggest that the CD8+ memory T cells enriched in breast milk, even after potential lysis in the infant gut, may represent a mechanism for passive transfer of cellular immunity from mother to child.