An interesting new study compares the phenotype and expression diversity of T cells in breast milk and peripheral blood against the backdrop of the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).
Study: Mucosal memory T cells in breast milk are modulated by SARS-CoV-2 mRNA vaccination. Image source: New Africa / Shutterstock
background
Breast milk contains hundreds of thousands of white blood cells from the mother’s immune system. About a tenth of these are T cells, which are most abundant at birth but then decline in the first month of extrauterine life until they reach a stable state. You will then stay at this level for about two years.
Breast milk T cells (BMTC) differ from those in peripheral blood in their increased levels of mucosal and effector memory markers. In addition, BMTC numbers increase when the mother or child is infected.
These cells can also migrate across the intestinal wall, taking advantage of the infant’s high intestinal permeability and surviving gastric acid (which is the lowest at this point) to reach the mesenteric lymph nodes, liver, spleen, and lungs for maternal passive to transfer immunity to the infant. While this has been observed in animal models, the same phenomenon called maternal microchimerism has not yet been demonstrated in humans.
A recent study by the current researchers showed that maternal microchimerism in human infants increased during the first three months of life in breastfed infants, in which case these mother’s BMTC could help passively protect the infant.
The focus of the current study, which was published on the preprint server medRxiv *, was to compare the BMTC spectrum with that in the peripheral blood and, secondly, to examine whether BMTC-specific for SARS-CoV-2 in breast milk Spikes are present after vaccination with the messenger ribonucleic acid (mRNA) vaccines, which are known to trigger a strong adaptive cellular immune response in the peripheral blood.
The study
The researchers examined the different types of T cells found in breast milk and found that, on the one hand, breast milk contains a higher concentration of antigen-experienced T cells than peripheral blood. These cells have high levels of expression of mucosal homing markers such as CCR9 that develop over time.
In comparison to the peripheral blood, breast milk is enriched in antigen-experienced T cells, both T effector and central memory populations. In addition, the T cell receptor (TCR) repertoire of BMC is very diverse, with several clonotypes abundant, although few of them have also been found in peripheral blood
The abundant clones showed a broad spectrum of TCRβ, indicating that they expressed different receptor structures and epitopes. In addition, the researchers found that these abundant clones were mostly private, meaning that they were unique to a single individual. However, the clonotypes did not separate from each individual, suggesting that each individual had a unique, structurally distinct set of abundant clonotypes.
Overall, the results suggest that excessive breast milk T cell clones are structurally diverse and respond to a range of pathogen-specific epitopes. BMTC also contained a TCRβ repertoire that was limited to the SARS-CoV-2 spike antigen.
In fact, 13/16 BMTCs showed TCRβ, which was likely spike-specific. When compared with paired peripheral blood samples, in which at least one clone in each sample was spike-specific, these spike-specific cells were almost 2-fold enriched in breast milk compared to peripheral blood.
After some women were given the third booster dose, their pre-vaccination breast milk samples were compared to samples taken three weeks later. The later samples showed a much larger percentage of spike-specific activated CD8 + tetramer positive T cells, indicating that they were recently recruited or activated. This confirmed the activation response of spike-specific T cells in breast milk in vivo when it was restimulated with the spike antigen after mRNA vaccination.
effects
The study shows that the T cells in breast milk are almost exclusively memory cells belonging to either the central memory or the effector cell phenotype. They show a high expression of mucosal homing markers with a diverse but different TCRβ repertoire compared to T cells in peripheral blood. Some clonotypes were very common, albeit very different.
The diverse TCRβ repertoire in BMTC with little overlap with the peripheral blood T cells may be due to the changed distribution of naive versus antigen-exposed cells, but with a broadly different response in each compartment among the memory T cells.
These abundant clones appeared to group across individuals, suggesting the presence of a common mucosal TCR repertoire in breast milk. Some clones were specific for the SARS-CoV-2 spike protein in the breast milk of vaccinated women.
The high effector memory T-cell counts found in this study with mucosal homing markers are consistent with an earlier study in people with or without HIV (human immunodeficiency virus) infection. The source of BMTC could be from a tissue-resident population in the breast tissue rather than from the peripheral blood through micro-injuries to the blood vessels.
In addition, the increased expression of CCR9 on the BMTCs with time since birth or since the second dose of vaccine suggests that local mucosal immunity at the breast level is developing over time. As more antigen is carried into the breast, for example from breast milk, or when resident tissue T cells spread due to their stimulation by the antigen, the T cell populations of the mucous membrane increase.
There might be an enteromammary axis, in short, a thesis also supported by the high concentrations of CCR9 and CD103 mucosal markers from BMTC. These cells can enter the infant’s airways and intestines after breastfeeding.
The restimulation response of BMTC, which suggests the migration of vaccine-activated T cells to mucosal sites, points to the underestimated potential of the breast as a site of mucosal immunity and could expand the field of vaccine research. While the mRNA vaccines were primarily studied for their T-cell responses in the peripheral blood, the virus actually hits the airways.
However, nasal and oropharyngeal swabs are difficult to obtain compared to breast milk samples. Until a correlation between the respiratory tract and breast milk samples with regard to the resident T-cell response is established, it is possible that one day breast milk samples will be used to characterize broad mucosal immunity after vaccination.
*Important NOTE
medRxiv publishes preliminary scientific reports, which are not peer-reviewed and therefore should not be considered conclusive, that guide clinical practice / health-related behavior or are treated as established information.
