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Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation
Fertility and Sterility ( IF 6.6 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.fertnstert.2019.12.022
Tao Zhang 1 , Wenyue Zhu 1 , Yiwei Zhao 1 , Wing Ching Cheung 1 , Yingyu Liu 1 , Xiaoyan Chen 1 , Yan Du 2 , Kam Tong Leung 3 , Yiu Leung Chan 1 , Chi Chiu Wang 4 , Susan Laird 5 , Tin Chiu Li 1
Affiliation  

OBJECTIVE To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive. DESIGN Prospective observational study. SETTING University teaching hospital. PATIENTS(S) Fifty-one infertile women undergoing day-5 blastocyst transfer. INTERVENTION(S) Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA. MAIN OUTCOME MEASURE(S) Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women. RESULT(S) In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3+NK-like T cells, Tim-3+/PD-1+CD8+ T cells, and Tim-3+/PD-1+CD4+ T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3+CD56dimNK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3+CD56brightNK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9. CONCLUSION(S) Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9.

中文翻译:

囊胚移植后外周血淋巴细胞中免疫检查点蛋白 T 细胞免疫球蛋白 mucin-3 和程序性细胞死亡-1 的早期瞬时抑制与成功植入有关

目的比较免疫检查点蛋白T细胞免疫球蛋白粘蛋白-3(Tim-3)/半乳糖凝集素-9(Gal-9)和程序性细胞死亡-1(PD-1)/程序性死亡配体1的外周水平变化(PD-L1)在怀孕和未怀孕的女性之间进行囊胚移植后的 9 天期间。设计前瞻性观察研究。设置大学教学医院。患者 (S) 51 名接受第 5 天囊胚移植的不孕妇女。干预措施 在胚胎移植 (ET) 当天以及之后 3、6 和 9 天获得的系列血样,用于通过流式细胞术测量各种外周淋巴细胞的膜性 Tim-3 和 PD-1 表达,以及血清浓度配体 Gal-9 和 PD-L1 通过 ELISA。主要观察指标 淋巴细胞上的膜 Tim-3 和 PD-1 表达以及血清 Gal-9 和 PD-L1 浓度以及孕妇和非孕妇之间的结果比较。结果(S)在受孕女性中,测量结果显示出三种不同类型的反应:[1] Tim-3+NK 样 T 细胞、Tim-3+/PD-1+CD8+ T 细胞的瞬时和统计学显着减少和在 ET 后 9 天恢复到基线水平的 Tim-3+/PD-1+CD4+ T 细胞;[2] 在第 9 天(Tim-3+CD56dimNK 细胞)减少后稳定增加至基线水平以上;[3] ET 后表达稳定增加,达到统计学显着高于第 9 天的基线水平(Tim-3+CD56brightNK 细胞)。
更新日期:2020-08-01
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