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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
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Metabolic Blockade of Glycolysis Diminishes Autoreactive CD4 T-Cell Effector Responses in Type 1 Diabetes

Miranda D Chávez1,2, Anna R Mahr1, Heather M Wilkins3,4,5

  • 1Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS.

Diabetes
|August 3, 2026
PubMed
Abstract

Insights

Inhibiting glycolysis with 2-deoxyglucose (2-DG) in autoreactive CD4 T cells delayed type 1 diabetes in mice. This approach reduced inflammatory responses and promoted immune tolerance, suggesting potential therapeutic applications.

Area of Science:

  • Immunology
  • Metabolic pathways in immune cells
  • Autoimmune diseases

Background:

  • Type 1 diabetes is an autoimmune disease characterized by the destruction of pancreatic beta cells by autoreactive T cells.
  • Glycolysis is a key metabolic pathway that fuels T cell activation and effector functions.
  • Targeting T cell metabolism offers a potential strategy for modulating immune responses in autoimmune diseases.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting glycolysis with 2-deoxyglucose (2-DG) in autoreactive CD4 T cells.
  • To determine the effects of 2-DG on T cell activation, differentiation, and the development of spontaneous type 1 diabetes in non-obese diabetic (NOD) mice.

Main Methods:

  • NOD mice were treated with 2-DG during the activation and differentiation of autoreactive CD4 T cells.
  • Flow cytometry and cytokine analysis were used to assess T cell phenotypes, effector functions, and anergic markers.
  • Disease progression and the onset of type 1 diabetes were monitored.

Main Results:

  • 2-DG treatment decreased effector responses, including interferon-gamma production, in autoreactive CD4 T cells.
  • 2-DG increased the expression of anergic markers such as CD73 and folate receptor 4.
  • Inhibition of glycolysis delayed the onset of spontaneous type 1 diabetes in NOD mice.
  • 2-DG reduced CD86 expression on antigen-presenting cells, potentially contributing to T cell anergy induction.

Conclusions:

  • Inhibiting glycolysis in autoreactive CD4 T cells is sufficient to diminish their pathogenic responses.
  • 2-DG treatment can delay type 1 diabetes development in a preclinical model.
  • Targeting T cell glycolysis represents a promising therapeutic strategy for T cell-mediated inflammatory diseases, including type 1 diabetes.

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