Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy.

Human γδ T cells are enriched at the maternal-fetal interface (MFI, decidua basalis) showing a highly differentiated phenotype. However, their functional potential is not well-known and it is not clear whether this decidua-enrichment is associated with specific γδ T cell receptors (TCR) as is observed in mice. Here we addressed these open questions by investigating decidual γδ T cells during early and late gestation, in comparison with paired blood samples, with flow cytometry (cytotoxic mediators, cytokines) and TCR high-throughput sequencing. While decidual γδ T cells expressed less perforin than their counterparts in the blood, they expressed significant more granulysin during early pregnancy. Strikingly, this high granulysin expression was limited to early pregnancy, as it was reduced at term pregnancy. In contrast to this granulysin expression pattern, decidual γδ T cells produced reduced levels of IFNγ and TNFα (compared to paired blood) in early pregnancy that then increased by term pregnancy. TCR repertoire analysis indicated that human decidual γδ T cells are not generated early in life as in the mouse. Despite this, a specific enrichment of the Vγ2 chain in the decidua in early pregnancy was observed that disappeared later onwards, reflecting dynamic changes in the decidual γδ TCR repertoire during human gestation. In conclusion, our data indicate that decidual γδ T cells express a specific and dynamic pattern of cytotoxic mediators, Th1 cytokines and TCR repertoire suggesting an important role for these unconventional T cells in assuring a healthy pregnancy in human.

Mother-to-newborn transmission of mycobacterial L-forms and Vδ2 T-cell response in placentobiome of BCG-vaccinated pregnant women.

The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L bacterial forms are extremely scarce. Bacille Calmette-Guérin is an attenuated strain of M. bovis and the only licensed vaccine used for tuberculosis prevention. We already have shown that filterable L-forms of BCG exist freely in the vaccine and are able to reproduce and to form colonies. The present study was focused on the placental microbiome in the context of mother's BCG vaccination. Here we report an isolation of filterable mycobacterial L-form cultures from gestational tissues and blood of healthy newborns delivered by healthy BCG-vaccinated mothers after normal pregnancy. Of note, vertically transmitted mycobacterial L-forms as a part of placentobiome of the pregnant women didn't influence the number of resident pathogen-reactive Vδ2 cells. Placenta colonization with mycobacterial L-forms occurs by maternal blood-to-decidua transfer very early in gestation. Together, these data showed that BCG L-forms have the capacity to pass trans-placental barrier and that maternal BCG vaccination affects the placentobiome.