The Role of Hyperglycemia in CD4 T Cell Survival and Differentiation

Abstract

The major driving force in the pathogenesis of pre-diabetes and Type 2 Diabetes is thought to be chronic and low grade systemic inflammation. Immune cells are key players in the induction of this chronic inflammation; however, the type of immune cells and mechanisms underlying the rapidly progressing pathogenesis of this disease are unclear. Therefore, we examined whether hyperglycemia alters CD4 T cell activation, differentiation and survival. Dendritic cells and T cells were isolated from human peripheral blood and cultured with varying amounts of glucose. Using flow cytometry we found dendritic cells primed in hyperglycemic conditions induced CD4 T cells to exhibit a more activated phenotype capable of mobilization. This was evident by upregulation of the adhesion molecule CD11a. Additionally, these activated CD4 T cells had a lower degree of proliferation and decreased expression of the apoptotic protein caspase-3 compared to CD4 T cells primed by dendritic cells stimulated with a physiological concentration of glucose. We conclude that hyperglycemia drives CD4 T cells towards an activated immunophenotype, which could be assessed via flow cytometry in the clinic to further stratify patients with prediabetes and Type 2 Diabetes and potentially predict those patients at highest risk for progression of the disease.