They explain how the immune system prepares for breastfeeding

Millions of babies begin breastfeeding during their first month of life. Breastfeeding has recognized benefits for both mother and child, reducing the maternal risk of breast and ovarian cancer, type 2 diabetes, and high blood pressure, while strengthening the baby's nutrition and immune system. However, because pregnancy and breastfeeding have historically been understudied, the scientific basis for many of these benefits remains unknown.

Now, a team of immunologists from the Salk Institute (USA) appear to have made progress in understanding the mechanisms of this complex process.

Based on animal research and samples of breast milk and tissue, the researchers discovered that immune cells called T cells are abundant in mammary glands during pregnancy and lactation, and some relocate from the gut. These cells likely contribute to maternal and infant health.

The findings, published in Nature Immunology, may help explain the benefits of breastfeeding, spur new solutions for mothers who cannot breastfeed, and inform dietary choices that improve breast milk production and quality.

"By investigating how immune cells change during pregnancy and lactation, we were able to find, for example, that there is a significant increase in immune cells in breast tissue during lactation, a process that requires the presence of bacteria," explains Deepshika Ramanan, lead author of the study.

Most studies on breastfeeding focus on the relationship between milk content and infant health. These studies have shown that babies receive significant amounts of gut bacteria and antibodies from their mothers through breast milk, which lays the fundamental foundation for the development of their immune systems. However, much less is known about the changes that a mother's body undergoes during this period.

Some characteristics of the mammary gland's immune system can be inferred from research on milk content. For example, the presence of antibodies in breast milk implies the presence of antibody-producing immune cells, called B lymphocytes. However, few have directly studied the activity of immune cells within the mammary gland itself.

"What's really exciting is that we not only found an increased presence of T cells in the mammary glands, but we discovered that some of these T cells came from the gut," says Abigail Jaquish, a researcher in Ramanan's lab. "We think they're likely supporting the breast tissue in the same way they normally do gut tissue."

The team analyzed mouse mammary glands before and after lactation and discovered an increase in three types of T lymphocytes (CD4+, CD8αα+, and CD8αβ+). These belong to intraepithelial lymphocytes, resident immune cells typical of mucosal tissues such as the intestines and lungs. These cells were observed to coat the mammary epithelium and present proteins characteristic of the intestine, suggesting their migration from there. These changes transform the mammary gland into a tissue with mucosal characteristics, preparing it for external exposure during lactation.

But did this also happen in humans? A search of databases of human breast tissue and milk samples revealed that it did: the human equivalents of these intraepithelial lymphocytes showed the same tendencies.

To determine whether microbes affected these mammary gland T cells in the same way as in the gut, the researchers compared the mammary glands of mice living in normal, germ-free environments and found that all three T cell subtypes were significantly more expressed in the microbe-exposed mice. This finding suggests that maternal microbes modulate the number of T cells created during lactation, which in turn could affect the resilience of the mammary gland's immune barrier.

"We now know much more about how the maternal immune system changes during this critical period," Ramanan says, "and we can use this information to begin exploring the direct effects of these immune cells on maternal and infant health."

Researchers hypothesize that hormones influence these numerous changes, and that the overall goal is to protect the mother from the outside world and associated infections. But understanding how they influence lactogenesis, milk quality, and maternal and infant health will be the next step.

Understanding the changes in maternal immune cells during pregnancy and breastfeeding can influence generations, as the transfer of immunity and the microbiome from mother to child is repeated over and over again. This knowledge could also lead to solutions for mothers who are unable to breastfeed, either through therapies that support natural milk production or more sophisticated formulas that provide some of the same immune support.