Augmented MHC Class I on Professional Antigen-Presenting Cells and Enhanced Cytokine Production by CD8(+) T Cells in Type 2 Diabetes Mellitus

2型糖尿病中专业抗原呈递细胞上MHC I类分子的增强和CD8(+) T细胞细胞因子产生增强

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Abstract

Effective antigen presentation by major histocompatibility complex (MHC) molecules to T cells is crucial for adaptive immunity. In type 2 diabetes mellitus (T2DM), metabolic dysregulation and chronic inflammation may impair these processes. We conducted a cross-sectional study to compare immune phenotypes between people with T2DM and healthy controls, and to correlate these findings with clinical parameters. People with T2DM exhibited augmented MHC I levels on B cells and CD14(+) monocytes, and a shift in T cell polarization toward proinflammatory phenotypes. This was characterized by increased frequencies of type 1 cytotoxic T (Tc1) cells, and higher production of interferon-gamma (IFN-γ) and interleukin (IL)-10 by CD8(+) T cells. Additionally, people with T2DM had higher frequencies of CD28(+) and IFN-γ(+) CD4(+) T cells, and elevated expression of CD28, IFN-γ, IL-10, and IL-17A by CD4(+) T cells. The shift toward a Tc1 phenotype correlated positively with blood glucose and negatively with insulin levels. Likewise, Th1 cell frequencies and IL-17 production by CD4(+) T cells correlated positively with blood glucose, while IL-10(+)CD4(+) T cell percentages correlated positively with insulin levels. Our findings suggest that T2DM is associated with a proinflammatory T-cell profile, polarization of which is linked to metabolic parameters.

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