Pregnancy is a state of immune tolerance that prevents maternal rejection of the fetus. Type 2 diabetes and obesity are associated with activation of the innate and adaptive immune system, with a low ratio of T regulatory (Treg) cells (immunomodulatory) to Th17 cells (proinflammatory). Alterations in T cell subsets have not been clearly elucidated in gestational diabetes (GDM) and previous studies have not employed weight-matched controls. We hypothesise that GDM is associated with a decreased immunoregulatory and an increased proinflammatory T cell phenotype compared to normoglycemic women with similar BMI.
AIM: To examine peripheral blood CD4 T cell subsets in women with GDM compared to normoglycemic women with similar BMI.
METHODS: Blood was collected at 36 weeks gestation in women with and without GDM in our antenatal clinic. Exclusion criteria included multiple pregnancy, preeclampsia/hypertension, immunosuppressive medication and autoimmune disease. Controls were matched for age and BMI. Using 9-colour flow cytometry, we compared the frequencies of circulating CD4(+) Th1, Th2, Th17 and Treg cells.
RESULTS:. There were 15 GDM and 13 control women (prepregnancy BMI 25.6±6.4 vs 25.1±6.3kg/m2 p=0.99). GDM women had a lower Treg:Th17 ratio (1.17±0.51 vs 1.81±0.96, p=0.03). Tregs were non significantly lower, and Th17 cells were non significantly higher in GDM. Pooling all women, there was a positive correlation between BMI and Th1 cell counts (r2=0.26, p=0.006) and a negative correlation with BMI and naïve Tregs (% of total Tregs)(r2=0.18, p=0.02), while the proportions of these, per se, were not different in GDM women. (Data expressed as means±SD).
CONCLUSIONS: These results suggest that increased maternal immune tolerance in pregnancy is less pronounced in GDM women compared to BMI-matched controls. While increasing BMI was associated with a proinflammatory CD4 T cell phenotype, the changes associated with GDM did not appear to be solely attributable to increased BMI.