Fatemi Ramina, Mirzadegan Ebrahim, Vahedian Zohreh, Zarnani Amir Hassan, Jeddi-Tehrani Mahmood, Idali Farah
Reproductive Immunology Research center, Avicenna Research Institute, ACECR, Tehran, Iran.
Iran J Immunol. 2017 Jun;14(2):159-171.
17β-estradiol (E2) has been known to modulate immune response. Recent studies indicate that E2 at pregnancy level plays a role in regulating T cell response.
To investigate the optimum dose of E2 (from 10-9 to 10-7 M) in mediating the generation of regulatory T cells (Tregs), using naive human CD4+ T cells from healthy women.
Naive peripheral T cells were purified and conditioned with soluble anti-CD28 in anti-CD3-coated plates in the presence or absence of E2. Flow cytometry was employed to assess the expression pattern of forkhead boxP3 (FOXP3) and programmed death-1 (PD-1). Proliferation and cytokine secretions were analyzed, using XTT and ELISA assays.
In the presence of different doses of E2, the expression levels of anti-CD3/CD28 antibody-stimulated CD25/ FOXP3 and FOXP3/PD-1 in conditioned T cells (cT) were peaked at 1 ng/ml (early pregnancy level, E2(1)) (47.14% (37.3-74.9) and 32% (27.7-52.5), respectively) and a slight, but not significant, increase after declining at 36 ng/ml (late pregnancy/pharmaceutical, E2(36)) (19.4% (15.2-24.5) and 15.8% (10.6-26.8), respectively). E2(1) cT showed a significantly reduced proliferation capacity (p<0.05) and secretion of IL-10 was enhanced in supernatants of E2(1 and 36) cT (p<0.05). In contrast to decreased TNF-α and IFN-γ secretions in E2(1) cT supernatants, E2(36) stimulated TNF-α and IFN-γ secretions (p<0.05 and p<0.01, respectively).
Our results indicate that the differential effect of E2 on generation of Tregs is consistent with the possibility that lower levels of pregnancy E2 are most efficient in induction of Tregs.
已知17β-雌二醇（E2）可调节免疫反应。最近的研究表明，妊娠水平的E2在调节T细胞反应中起作用。
使用健康女性的初始人CD4+T细胞，研究E2（浓度范围为10-9至10-7M）介导调节性T细胞（Tregs）生成的最佳剂量。
在有或无E2存在的情况下，将初始外周血T细胞纯化后在包被抗CD3的培养板中用可溶性抗CD28进行预处理。采用流式细胞术评估叉头框蛋白P3（FOXP3）和程序性死亡蛋白1（PD-1）的表达模式。使用XTT和ELISA检测分析细胞增殖和细胞因子分泌情况。
在不同剂量E2存在的情况下，经抗CD3/CD28抗体刺激的条件性T细胞（cT）中，CD25/FOXP3和FOXP3/PD-1的表达水平在1ng/ml（妊娠早期水平，E2(1)）时达到峰值（分别为47.14%（37.3 - 74.9）和32%（27.7 - 52.5）），在36ng/ml（妊娠晚期/药物剂量，E2(36)）时下降后略有但不显著的增加（分别为19.4%（15.2 - 24.5）和15.8%（10.6 - 26.8））。E2(1) cT显示增殖能力显著降低（p<0.05），E2(1和36) cT的上清液中IL-10分泌增加（p<0.05）。与E2(1) cT上清液中TNF-α和IFN-γ分泌减少相反，E2(36)刺激TNF-α和IFN-γ分泌（分别为p<0.05和p<0.01）。
我们的结果表明，E2对Tregs生成的不同影响与较低水平的妊娠E2在诱导Tregs方面最有效的可能性一致。
