Menopausal status influences the expression of programmed death (PD)-1 and its ligand PD-L1 on immune cells from the human female reproductive tract.

Problem: The programmed death 1 (PD-1)/PD-L1 pathway regulates peripheral tolerance, immune responses, and is up-regulated in chronic viral infections, including HIV infection. However, expression of PD-1/PD-L1 on immune cells from the human female reproductive tract (FRT) and possible regulation by menopause and sex hormones are poorly understood.

Method Of Study: PD-1/PD-L1 expression was analyzed on CD4(+) and CD8(+) T cells, CD163(+) macrophages, and CD11c(+) dendritic cells (DC) from endometrium (EM), endocervix (CX) and ectocervix (ECX). Expression after hormone treatment in culture was also evaluated.

Results: PD-1 and PD-L1 were constitutively expressed on CD4(+) and CD8(+) T cells from the FRT. PD-L1(+) CD4(+) T cells were increased in CX compared to EM and ECX, while no differences were found for PD-1 or between CD8(+) T cells from different sites. Macrophages and DCs constitutively expressed PD-L1, but not PD-1, with no differences observed between FRT sites. Pre-menopausal FRT tissues showed increased PD-L1 expression on CD8(+) T cells, but decreased expression on DCs when compared to post-menopausal women. In vitro estradiol treatment up-regulated PD-L1 expression specifically on CD8(+) T cells from CX, but had no effect on PD-1/PD-L1 expression on the other cell types.

Conclusion: Our results suggest that PD-L1 may be involved in the differential regulation of FRT immune responses between pre-menopausal and post-menopausal women.