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



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.



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.



Our results suggest that PD-L1 may be involved in the differential regulation of FRT immune responses between pre-menopausal and post-menopausal women.
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Zheng
Z
Shen
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Marta
M
Rodriguez-Garcia
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Mickey V
MV
Patel
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Fiona D
FD
Barr
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Charles R
CR
Wira
D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
CD4+ T cells; CD8+ T cells; PD-1/PD-L1, post-menopausal; dendritic cells; sex hormones