Immunoregulatory molecules in patients with gestational diabetes mellitus

Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case–control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4⁺ and CD8⁺), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4⁺CD69⁺ and CD8⁺CD69⁺ T cells; only patients with insulin-treated GDM had increased numbers of CD4⁺HLA-DR⁺ T cells. We also observed significantly higher percentages of CD4⁺CD28⁺HLA-DR⁺, CD3⁺CD4⁺ICOS⁺, CD3⁺CD4⁺PD-1⁺, CD8⁺CD28⁺CD69⁺, CD8⁺CD28⁺HLA-DR⁺, CD8⁺CTLA-4⁺HLA-DR⁺, and CD3⁺CD8⁺ICOS⁺ T cells and lower frequency of CD3⁺CD4⁺CTLA-4⁺, CD3⁺CD8⁺CTLA-4⁺, and CD8⁺ICOS⁺HLA-DR⁺ T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.