Reproduction Medical Center, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, PR China; Reproduction Medical Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, Yantai 264000, PR China.
Department of Clinical Laboratory, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, Yantai 264000, PR China; School of Medicine, Qingdao Universityō, 38 Dengzhou Road, Qingdao 266000, PR China.
J Reprod Immunol. 2022 Dec;154:103694. doi: 10.1016/j.jri.2022.103694. Epub 2022 Aug 17.
Regulatory T cells (Tregs) proliferate after encountering the fetal antigen, which plays an important role in maintaining maternal-fetal tolerance. Activated Tregs increase number and function after antigen encounter and develop memory. Upon subsequent antigen exposure, Treg cells re-expand more rapidly. However, the characteristics of memory regulatory T cells (mTregs) during normal pregnancy and unexplained recurrent pregnancy loss (URPL) have not been elucidated well. In this study, we analyzed the proportion of Tregs and mTregs in the peripheral blood and their surface expression of PD-1, CCR6, and HLA-G in normal non-pregnant (n = 20) and pregnant (n = 20) women, and non-pregnant (n = 20) and pregnant URPL (n = 20) women. We found that the proportions of mTregs in lymphocytes, CD3 T cells, CD4 T cells, and Tregs were lower in pregnant URPL patients than in normal pregnant women. The proportions of CD4CD45RO Th cells in lymphocytes, CD3 T, and CD4 T cells in the pregnant URPL group were the highest among the four groups (P < 0.05). There were no significant differences among the other three groups (P > 0.05). The proportions of CD4/CCR6/mTregs, CD4/PD1/mTregs, CD4/HLA-GmTregs were significantly lower in the non-pregnant normal group and non-pregnant URPL group than in normal pregnant group and pregnant URPL group (P < 0.05, respectively). The proportions of CD4/CCR6 mTregs, CD4/PD-1/mTregs CD4HLA-G/mTregs were lower in pregnant URPL group than in normal pregnant group (P < 0.05, respectively). These findings indicate that fetal antigen-specific mTregs play an important role in pregnancy maintenance, and the dysregulation of mTreg may contribute to URPL.
调节性 T 细胞（Tregs）在遇到胎儿抗原后增殖，这在维持母婴耐受中起着重要作用。Tregs 在抗原接触后增加数量和功能，并发展为记忆细胞。在随后的抗原暴露后，Treg 细胞更快地重新扩增。然而，在正常妊娠和不明原因的复发性妊娠丢失（URPL）中，记忆调节性 T 细胞（mTregs）的特征尚未得到很好的阐明。在这项研究中，我们分析了外周血中 Tregs 和 mTregs 的比例及其表面 PD-1、CCR6 和 HLA-G 的表达，在正常非妊娠（n=20）和妊娠（n=20）女性以及非妊娠 URPL（n=20）和妊娠 URPL（n=20）女性。我们发现，与正常妊娠妇女相比，妊娠 URPL 患者淋巴细胞、CD3 T 细胞、CD4 T 细胞和 Tregs 中的 mTregs 比例较低。淋巴细胞、CD3 T 和 CD4 T 细胞中 CD4CD45RO Th 细胞的比例在妊娠 URPL 组中最高（P<0.05）。其他三组之间没有显著差异（P>0.05）。非妊娠正常组和非妊娠 URPL 组的 CD4/CCR6/mTregs、CD4/PD1/mTregs、CD4/HLA-GmTregs 比例明显低于正常妊娠组和妊娠 URPL 组（P<0.05）。妊娠 URPL 组的 CD4/CCR6 mTregs、CD4/PD-1/mTregs CD4HLA-G/mTregs 比例低于正常妊娠组（P<0.05）。这些发现表明，胎儿抗原特异性 mTregs 在维持妊娠中起着重要作用，mTreg 的失调可能导致 URPL。
