PD-1 and PD-L1 expression on T-cell subsets in women with unexplained recurrent pregnancy losses

Abstract

Problem: Does programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) expression on the T-cell subsets such as T helper (Th) 1, Th17, and Treg cells differentiate women with recurrent pregnancy losses (RPL) from normal fertile women?

Method of study: The study was designed as a prospective cohort study. Forty-five women with two or more RPL of unknown etiology and twenty fertile women who had at least one or more live-born infants were enrolled prospectively from Jan 2017 to Jul 2019. PD-1 and PD-L1 expression on T-cell subsets were measured by flow cytometric analysis.

Results: The proportions of PD-1⁺ Th1 (CD4⁺ /IFN-γ⁺ /CD279⁺ and CD4⁺ /TNF-α⁺ /CD279⁺ ) and PD-1⁺ Th17 cells (CD4⁺ /IL17⁺ /CD279⁺ ) were significantly lower in RPL group than those of controls (P < .05, respectively). The proportion of PD-1⁺ Tregs (CD4⁺ /CD25⁺ /CD127^dim/- /CD279⁺ ) in RPL group was not different from that of controls. The proportion of PD-L1⁺ Th17 cells (CD4⁺ IL17⁺ CD274⁺ ) was significantly lower as compared with that of /controls (P < .05). However, the proportions of PD-L1⁺ Th1 (CD4⁺ /IFN-γ⁺ /CD274⁺ and CD4⁺ /TNF-α⁺ /CD274⁺ ) and PD-L1⁺ Treg (CD4⁺ /CD25⁺ /CD127^dim/- /CD274⁺ ) cells were not different between the RPL group and controls (P > .05, respectively). In Th1, Th17 and Treg cells, the proportions of PD-L1⁺ (CD274⁺ ) cells were significantly higher than those of PD-1⁺ (CD279⁺ ) cells in both RPL group and controls (P < .05, respectively).

Conclusion: PD-1 and PD-L1 expressions on Th17 cells as well as PD-1 expression on Th1 cells were significantly downregulated in women with RPL, which may lead to increased Th1 and Th17 immunity, and imbalance between Th17, Th1, and Treg cells in women with RPL.

Keywords: PD-1/PD-L1; RPL; Th1 cells; Th17 cells.