Expression and significance of PD-1/PDL-1 in T cells, Treg and Breg cells of patients with unexplained recurrent abortion
10.3760/cma.j.cn114452-20230912-00135
- VernacularTitle:PD-1/PDL-1在原因不明复发性流产患者T细胞、Tregs和Bregs细胞中的表达及意义
- Author:
Baoguo CHEN
1
;
Jun GAN
;
Rui ZHENG
;
Weiguo ZHANG
;
Yini YU
Author Information
1. 温州医科大学附属台州医院中心实验室，临海 317000
- Keywords:
Recurrent abortion;
Programmed cell death 1 receptor;
Programmed death-ligand 1;
B-lymphocytes, regulatory;
T-lymphocytes, regulatory
- From:
Chinese Journal of Laboratory Medicine
2024;47(6):678-685
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the expression levels and significance of programmed death factor 1 (PD-1)/programmed death factor ligand 1 (PDL-1) in T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs) in patients with unexplained recurrent spontaneous abortion (URSA).Methods:Forty-two URSA patients (as patient group), 34 healthy pregnant women (as normal pregnancy group) and 30 unpregnant healthy examination patients (as control group) were collected for retrospective analysis,all study subjects were from patients who were treated in Taizhou Hospital affiliated to Wenzhou Medical University from February 2020 to February 2022. Flow cytometry was used to detect the expression level of PD-1/PDL-1 in Treg cells, Breg cells and [T cells, B cells and natural killer cells (TBNK)] lymphocyte subsets, as well as the expression level of serum Th1 (IFN-γ, TNF-α)/Th2 (IL-4, IL-6, IL-10)/Th17 (IL-17) cytokine expression. The patients were treated with lymphocyte immunotherapy, the changes of PD-1/PDL-1 levels were detected at the end of treatment, and the pregnancy outcome was recorded during follow-up. Comparisons between multiple groups were performed by ANOVA, comparisons before and after treatment in URSA patients were performed by paired T-test, and correlation of each test index by bivariate correlation analysis.Results:The expression levels of PD-1/PDL-1 in Treg, Breg cells and T lymphocyte subsets in peripheral blood of patients with URSA was significantly lower than that of healthy pregnant women(all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was negatively correlated with the expression of serum Th1 cytokines Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) (The r values were -0.44, -0.85, -0.33, and -0.94, respectively, all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was positively correlated with the expression of serum Th2 cytokines interleukin 4(IL-4), interleukin 6(IL-6) and interleukin 10(IL-10)(The r values were 0.55, 0.47, 0.41, 0.33, 0.46, and 0.69, respectively,all P<0.01). The proportion of Breg cells and Treg cells were positively correlated with the level of serum IL-10 expression(The r values were 0.97, and 0.95 respectively, all P<0.01). The proportion of Treg cells was negatively correlated with the expression of IL-17( r=?0.95, P<0.01). The expression of PD-1/PDL-1 in Breg cells and Treg cells was positively correlated with the expression of serum IL-10(The r values were 0.95, 0.36, 0.96, and 0.95, respectively, all P<0.01). There was a negative correlation between serum IL-10 expression level and IL-17 expression level( r=?0.58, P<0.01). After URSA treatment, pregnancy was successful in 23 cases and failed in 19 cases. The expression of PD-1/PD-L1 on CD4, CD8, Tregs cells and Bregs cells in USRA treatment group was significantly higher than that before treatment( P<0.01), but there was no significant change in treatment failure group( P>0.05). Conclusion:The low expression of PD-1/PD-L1 in Treg cells, Breg cells and T cell subsets in peripheral blood of patients with URSA results in the immune imbalance of Th1/Th2 and Tregs/Th17, and the damage of maternal-fetal immune tolerance leads to pregnancy failure, which may be a potential therapeutic target.
