Gamma/Delta T Cells in the Course of Healthy Human Pregnancy: Cytotoxic Potential and the Tendency of CD8 Expression Make CD56+γδT Cells a Unique Lymphocyte Subset

To date, pregnancy is an immunological paradox. The semi-allogenic fetus must be accepted by the maternal immune system, while defense against pathogens and immune surveillance cannot be compromised. Gamma/delta T cells are believed to play an important role in this immunological puzzle. In this study, we analyzed peripheral blood CD56+ gamma delta T cells from pregnant women (1(st), 2(nd), and 3(rd) trimester) and non-pregnant women by multicolor flow cytometry. Interestingly, gamma delta T cells represent almost half of CD3+/CD56+ cells. Among gamma delta T cells, the CD56+ population expands in the 2(nd) and 3(rd) trimester. CD56+ gamma delta T cells maintained a predominantly CD4-/CD8- or CD8+ phenotype, while CD56- gamma delta T cells were in similar rates CD4-/CD8- or CD4+ during pregnancy. Investigation of the lysosomal degranulation marker CD107a revealed a preserved elevated rate of potentially cytotoxic CD56+ gamma delta T cells in pregnancy, while their cytotoxic strength was reduced. Furthermore, CD56+ gamma delta T cells continuously showed a higher prevalence of PD-1 expression. CD56+ gamma delta T cells' rate of PD-1 increased in the 1(st) trimester and decreased hereafter back to normal level. We correlated the cytotoxic potential and the expression of the inhibitory immune checkpoint PD-1 and were able to demonstrate that highly cytotoxic cells within this CD56+ gamma delta T population tend to express PD-1, which might allow the inhibition of these cells after binding its ligand in the placenta. These findings should support the understanding of the complex processes, which ensure the maintenance of pregnancy.

Automated summary

The study showed that during pregnancy, the proportion of CD56+ gamma delta T cells increases while maintaining potential cytotoxicity, although the cytotoxic strength is reduced, and PD-1 expression increases. Highly cytotoxic CD56+ gamma delta T cells tend to express PD-1, which may allow the inhibition of these cells after binding its ligand in the placenta.