The role of regulatory T cell ( T reg ) subsets in gestational diabetes mellitus

Summary 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 ( T reg ) differentiation for the development of GDM during pregnancy. We used six‐colour flow cytometric analysis to demonstrate that the total CD 4 + CD 127 low+/− CD 25 + forkhead box protein 3 ( F ox P 3 + ) T reg pool consists of four different T reg subsets: naive CD 45 RA + T regs , HLA‐DR − CD 45 RA − memory T regs ( DR − T regs ) and the highly differentiated and activated HLA ‐ DR low+ CD 45 RA − and HLA ‐ DR high+ CD 45 RA − memory T regs ( DR low+ and DR high+ T regs ). Compared to healthy pregnancies, the percentage of CD 4 + CD 127 low+/− CD 25 + F ox P 3 + T regs within the total CD 4 + T helper cell pool was not different in patients affected by GDM . However, the suppressive activity of the total CD 4 + CD 127 low+/− CD 25 + T reg pool was significantly reduced in GDM patients. The composition of the total T reg pool changed in the way that its percentage of naive CD 45 RA + T regs was decreased significantly in both patients with dietary‐adjusted GDM and patients with insulin‐dependent GDM . In contrast, the percentage of DR − ‐memory T regs was increased significantly in patients with dietary‐adjusted GDM , while the percentage of DR low+ and DR high+ memory T regs 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 T regs may cause the reduction of the suppressive capacity of the total T reg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.