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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Augmented MHC Class I on Professional Antigen-Presenting Cells and Enhanced Cytokine Production by CD8+ T Cells in
Shan Liu1,2, Tharushika Jayasinghe2, Daria Kamińska3
1Department of Endocrinology, the Second Affiliated Hospital, School of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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.
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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