The CD4+CD25 bright regulatory T cells and CTLA-4 expression in peripheral and decidual lymphocytes are down-regulated in human miscarriage.
The present study was undertaken to analyze the changes in the proportion of CD4(+)CD25(bright) regulatory T (Treg) cells and the expression of costimulatory molecules, CTLA-4 and CD28, in the peripheral blood and deciduas in the setting of non-pregnancy, normal early pregnancy and miscarriage. In this study, we showed that CD4(+)CD25(bright) T cells significantly increased in the peripheral of normal pregnancy compared to that of non-pregnancy. The proportions of CD4(+)CD25(bright) T cells in both peripheral blood and deciduas were significantly lower in miscarriage than that of normal pregnancy. CD4(+)CD25(bright) T cells were characterized by high-level FoxP3 expression and low-level CD69 expression. An increase in the CD28 mRNA expression was accompanied by a decrease in the CTLA-4 mRNA expression in decidual tissues from human miscarriage. The ratios of CTLA-4(+)/CD28(+) in miscarriage were significantly lower than that of the normal pregnancy both in the peripheral and in deciduas. The ratio of CTLA-4(+)/CD28(+) in CD4(+)CD25(bright) T cells was significantly higher than that of the CD4(+)CD25(dim) T cells both in normal pregnancy and in miscarriage. The decidual T cells in the miscarriage appeared higher in responsiveness and IL-2 and IFN-gamma production in comparison with the decidual T cells in the early pregnancy. These results above suggest that CD4(+)CD25(bright) Treg cells might play a role in the maintenance of pregnancy via up-regulation of CTLA-4 expression. The down-regulation of Treg cells and their functions, and the imbalance of positive and negative regulators of costimulatory signals might lead to an abnormal immune milieu, which confer susceptibility to pregnancy loss.
Jin
Li-Ping
LP
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
Chen
Qiao-Ying
QY
Zhang
Tai
T
Guo
Pei-Fen
PF
Li
Da-Jin
DJ
D000022:Abortion, Spontaneous / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen; D003656:Decidua / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D007371:Interferon-gamma