Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages—Preliminary Studies

Abstract

Background: Immune checkpoints are molecules that regulate the function of immune cells and control inflammation processes. An important role in this regard is played by TIM-3/Gal-9 and PD-1/PDL-1 interactions. Previous research performed in a mouse model of pregnancy loss confirmed that blocking TIM-3 could induce fetal loss. Similarly, the PD-1 molecule maintains protective interactions between the mother’s immune cells and the fetus. The purpose of this study was to assess the expression of these molecules on a range of T lymphocyte subpopulations from non-pregnant women with recurrent spontaneous abortion (RSA) versus healthy fertile women. Methods: PBMCs were isolated by gradient centrifugation of blood obtained from 12 healthy women and 24 women with RSA and immediately stained for flow cytometry analysis. Standard immunophenotyping of PBMC was performed with the antibodies against classical lymphocyte markers: CD3, CD4, CD8, and CD56. Immune checkpoints were investigated using antibodies against PD-1(CD279) and TIM-3(CD366). Results: We found that expression of TIM-3 was significantly decreased on CD8+ T lymphocytes in the RSA group, and expression of PD-1 was upregulated on CD4+ T lymphocytes in the RSA group in comparison to the healthy controls. Conclusions: Considering our findings, therapeutic intervention towards immune checkpoints may be a promising treatment option for recurrent spontaneous abortion.

Keywords

• immune checkpoints
• miscarriage
• pregnancy loss
• PD-1
• RSA
• recurrent spontaneous abortion