Transfer of Maternal Immune Cells by Breastfeeding: Maternal Cytotoxic T Lymphocytes Present in Breast Milk Localize in the Peyer’s Patches of the Nursed Infant

Abstract

Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer’s patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.

Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody

“…Cells were then treated, stained, and analyzed as in functional and migrate within the infant to the liver, thymus, spleen, and lymph nodes and lymphocytes, in particular, appear to home to Peyer's patches of the newborn's intestines. [28][29][30][31][32] Intact leukocytes certainly cross from the stomach of the infant despite the acidic environment and are likely an important defense against infection and possible key factors for teaching the newborn immune system, with at least 0.1% of cells ingested from milk infiltrating the peripheral tissues. 57 Notably, neutrophils of newborn humans during days 1-3 of life are functionally diminished compared with those of an adult, and deficiencies in newborn lymphocyte function have also been noted.…”

“…26 Various in vivo studies have demonstrated that maternal leukocytes provide critical immunity to the infant and are functional well beyond these sites of initial ingestion. 25,[27][28][29][30][31][32] All maternally derived cells ingested by the infant have the potential to perform immune functions alongside or to compensate for the infant's own leukocytes. 33 This is likely in conjunction with other BM components, such as maternal Abs.…”

Milk MicroRNAs in Health and Disease

“…So far, the bulk of evidence supports milk microRNA bioaccessibility (survivability) in the human consumers, either adults or infants. In infants, the digestive tract is far less developed and exerts less harsh conditions (lower acidity and low enzymatic activity), allowing even immune cells and, other cells of milk, to survive and settle within the infant digestive tract wall (Cabinian et al., ; Moles et al., ). Moreover, infants are only fed with breast milk or milk formulations during the first 6 months of their existence.…”

Breastmilk cell trafficking induces microchimerism‐mediated immune system maturation in the infant

“…With very few exceptions, all experiments on animal models were conducted during the period of intense gut permeability suggesting that milk lymphocytes are not only taken up by the breastfed offspring but that this process results in a transfer of immunologic information and enhances the early immune response . Interestingly, the experiments conducted in the study from Cabinian et al were reproducible in MHC‐mismatched animals, suggesting that breastmilk leukocytes may target infant PP independently of the MHC haplotype.…”