Abstract
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+ γδT cells from pregnant women (1st, 2nd, and 3rd trimester) and non-pregnant women by multicolor flow cytometry. Interestingly, γδT cells represent almost half of CD3+/CD56+ cells. Among γδT cells, the CD56+ population expands in the 2nd and 3rd trimester. CD56+ γδT cells maintained a predominantly CD4–/CD8– or CD8+ phenotype, while CD56– γδT 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+ γδT cells in pregnancy, while their cytotoxic strength was reduced. Furthermore, CD56+ γδT cells continuously showed a higher prevalence of PD-1 expression. CD56+ γδT cells’ rate of PD-1 increased in the 1st 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+ γδT 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.
Highlights
Gamma/delta T cells and their possible functions in pregnancy have been the scope of many investigations over the last decades
We found a small population of CD3+ lymphocytes, which was double-positive for gdTCR and CD56 but did not show any alterations in frequency during pregnancy or to the nonpregnant control (Figure 1A)
While abT cells are traditionally divided into CD4+ and CD8+ T cells, gdT cells are mainly classified based on their Vd-chainusage into circulating Vd2+ and resident Vd1+ cells
Summary
Gamma/delta T cells and their possible functions in pregnancy have been the scope of many investigations over the last decades This T cell population has a unique physiology, as it does not underlie MHC-restriction nor requires antigen processing [1, 2]. Data suggests the thymus as main source of gdT cells [4], experiments with athymic mice suggested that further development sites must exist [5]. Their Vd usage divides them into two major subsets, of which one is the Vd2 population whereas the other is often named as non-Vd2 population. As research is mainly focused on the TCR repertoire of gdT cells, the importance of these major co-receptors on gdT cells has not been investigated thoroughly
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