Evaluation of Percentage of Interferon-Gamma Secreting T Helper Cells and Expression of Related Genes in Patients with Type 2 Diabetes Mellitus

Abstract

Background and Objective: The alterations of the adaptive immune system are involved in type 2 diabetes mellitus (T2DM) pathogenesis. T helper 1 (Th1) cells or CD4 T cells are the pro-inflammatory components of adaptive immunity with the main feature of interferon-gamma (IFN-γ) secretion. The aim of this study was to evaluate the percentage of IFN-γ, assess the expression of related-genes in CD4 T cells, including T-bet, IRF1, RUNX3, and NFκB, and determine the correlation between them and clinical parameters in T2DM patients. Materials and Methods: In this case-control study, peripheral blood CD4 T cells were isolated from 40 patients and 40 healthy controls (HCs). The percentage of IFN-γ secreting CD4 T cells was assessed using flow cytometry, and the related-genes were evaluated using real-time polymerase chain reaction. Results: The percentage of IFN-γ secreting CD4 T cells significantly increased in the patients in comparison to that of the HCs (P<0.001). The expression levels of IRF1 and NFκB were higher in the patients in comparison to those of the HCs (P=0.02 and P<0.001, respectively). A significant positive correlation between IFN-γ secreting CD4 T cells and both IRF1 and NFκB was observed in the patients (P=0.001 and P=0.002, respectively). There was a significant positive correlation between IFN-γ secreting CD4 T cells, IRF1, and NFκB with fasting plasma glucose and hemoglobin A1c in the patients (P<0.001). Conclusion: Due to the increased response of Th1 cells (the production of IFN-γ and expression of related genes) in the patients and existing correlation between them and plasma glucose level, it seems that these inflammatory factors are involved in T2DM pathogenesis, and the use of IFN-γ pathway antagonists could be considered a novel therapeutic approach.