Functional Defects of Regulatory T Cell Through Interleukin 10 Mediated Mechanism in the Induction of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a metabolic and low-grade inflammatory disease most commonly found in pregnant women with high body mass index and non-Caucasian ethnicities; however, not all women of high-risk groups develop GDM. We hypothesized that regulatory T cells (Tregs) might present a role in suppressing GDM development. To this end, 55 high-risk women at early pregnancy (first trimester) were recruited, and 21 of them developed GDM while the other 34 did not. Compared to those subjects who did not develop GDM (non-GDM), the patients who developed GDM presented reduced levels of Tregs and elevated levels of serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). The Tregs in the GDM group also presented reduced levels of transforming growth factor beta and IL-10, compared with the non-GDM group. The frequency of circulating Tregs and serum TNF-alpha level were inversely correlated. In addition, addition of Tregs from non-GDM patients, but not those from GDM patients, significantly suppressed the interferon gamma and TNF-alpha production by effector T cells through IL-10-mediated mechanisms, suggesting a functional defect in Tregs from GDM subjects. Together, these data indicated that the presence of functional Tregs could protect the pregnant women from GDM development by suppressing pro-inflammatory responses and that the dysregulation of Tregs early in pregnancy elevated the risk of GDM.