Association between PD-1/PD-L1 and T regulate cells in early recurrent miscarriage.
In this study, we try to testify the relationship between the programmed cell death receptor-1 (PD-1)/programmed cell death ligand 1 (PD-L1) passway and Treg cells in maternal-fetal immune regulation through PD-1 blockade on lymphocytes of normal early pregnancy in vitro and investigation of the PD-1 and PD-L1 changes in early recurrent miscarriage patients. CD4+ CD25+ Treg cells and PD-1 (CD279) positive cell were detected in deciduas in early recurrent miscarriage patients by flow cytometry. And the normal early pregnant women were as controls. Meanwhile the mRNA level of PD-1 and molecular expression of PD-L1 in deciduas of early recurrent miscarriage patients were detected by real time RT-PCR test and Immunohistochemical staining respectively. Also through antibody blocking assay to block PD-1 on lymphocytes of normal early pregnancy in vitro further testify the relationship between PD-1/PD-L1 and Treg cells, the results were analyzed by flow cytometry. CD4+ CD25+ Treg cells decreased both in deciduas in RM (P < 0.05), and for all almost 100% Treg cells (CD4+ CD25+) expressed PD-1, but there was no difference between the PD-1 positive cells in decidual lymphocytes in RM and that in normal pregnancy women (P > 0.05). PD-L1 mRNA in deciduas decreased in RM (P < 0.001), but PD-1 mRNA no difference (P > 0.1). After PD-1 blockade there was no change in CD4+ CD25+ Treg cells percentage, while the CD4+ T cell percentage increased (P < 0.01), as well as the level of IFN-gamma in cells supernatant (P < 0.01). PD-1 blockade has a little influence on the number of Treg cells, and may lead to impaired Treg cells function, the decrease of PD-L1 may closely relates to the occurrence of early recurrent miscarriage and implies that Treg cells may through PD-1/PD-L1 pathway play a role of immunosuppression regulation, and the impairment of Treg cells function in recurrent early abortion cases may be due to PD-L1 decrease in deciduas or trophoblast cells rather than PD-1 change.
Department of Obstetrics, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China ; Department of Obstetrics, Shandong University Affiliated Shandong Provincial Hospital Jinan 250021, Shandong, China.
Guiyu
G
Li
Department of Obstetrics, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China.
Caixia
C
Lu
Department of Obstetrics, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China.
Jing
J
Gao
Department of Obstetrics, Shandong University Affiliated Shandong Provincial Hospital Jinan 250021, Shandong, China.
Xietong
X
Wang
Department of Clinical Laboratory, Shandong University Affiliated Shandong Provincial Hospital Jinan 250021, Shandong, China.
Huanling
H
Wu
Department of Obstetrics, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China.
Chao
C
Lee
Department of Obstetrics, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China.
Baoxiang
B
Xing
Department of Gynecology, Qingdao University Affiliated Hospital Qingdao 266000, Shandong, China.
Qi
Q
Zhang
D000026:Abortion, Habitual / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D060890:B7-H1 Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D003656:Decidua / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D011247:Pregnancy; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C573415:IFNG protein, human; C508609:IL10 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma
Early pregnancy; immunoregulation; miscarriage; programmed cell death receptor-1; regulatory T cells