The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus
The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus
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DOI：
10.1111/cei.12300
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发表时间：
2014-07-01
影响因子：
4.6
通讯作者：
Steinborn, A.
中科院分区：
文献类型：
--
作者：
Schober, L.;Radnai, D.;Steinborn, A.
正常妊娠期间的生理变化的特点是炎症免疫反应和胰岛素抵抗。因此，我们推测妊娠期糖尿病（GDM）可能是由母体免疫系统对妊娠的不适当适应引起的。在这项研究中，我们研究了调节性T细胞（Treg）分化在妊娠期GDM发展中的作用。我们使用六色流式细胞术分析来证明总的CD 4 + CD 127低+/-CD 25+叉头盒蛋白3（FoxP 3+）Treg池由四种不同的Treg亚群组成：初始CD 45 RA + Tcl 3、HLA-DR-CD 45 RA-记忆性Tcl 3（DR-Tcl 3）以及高度分化和活化的HLA-DR低+CD 45 RA-和HLA-DR高+CD 45 RA-记忆性Tcl 3（DR低+和DR高+Tcl 3）。与健康孕妇相比，GDM患者的总CD 4 + T辅助细胞库中CD 4 + CD 127 low +/-CD 25 + FoxP 3 + T细胞的百分比没有差异。然而，在GDM患者中，总CD 4 + CD 127 low +/-CD 25 + Treg池的抑制活性显著降低。总Treg库的组成发生变化，在饮食调整的GDM患者和胰岛素依赖性GDM患者中，初始CD 45 RA + Treg的百分比均显着下降。与此相反，饮食调整的GDM患者DR-记忆TdR的百分比显著增加，而胰岛素依赖型GDM患者DR低+和DR高+记忆TdR的百分比显著增加。因此，我们的研究结果表明，与幼稚和记忆性T细胞的发育和功能相关的稳态参数的改变可能导致GDM患者中总Treg池的抑制能力降低。然而，由于这是一项探索性分析，因此结果仅具有提示性，需要进一步验证。
Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4+CD127low+/-CD25+ forkhead box protein 3 (FoxP3+) Treg pool consists of four different Treg subsets: naive CD45RA+ Tregs, HLA-DR-CD45RA- memory Tregs (DR- Tregs) and the highly differentiated and activated HLA-DRlow+CD45RA- and HLA-DRhigh+CD45RA- memory Tregs (DRlow+ and DRhigh+ Tregs). Compared to healthy pregnancies, the percentage of CD4+CD127low+/-CD25+FoxP3+ Tregs within the total CD4+ T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4+CD127low+/-CD25+ Treg pool was significantly reduced in GDM patients. The composition of the total Treg pool changed in the way that its percentage of naive CD45RA+ Tregs was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR--memory Tregs was increased significantly in patients with dietary-adjusted GDM, while the percentage of DRlow+ and DRhigh+ memory Tregs was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory Tregs may cause the reduction of the suppressive capacity of the total Treg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.