Related Experiment Video

Updated: Apr 5, 2026

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
06:27

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

Published on: May 6, 2013

17.5K

Loss of NOX-Derived Superoxide Exacerbates Diabetogenic CD4 T-Cell Effector Responses in Type 1 Diabetes

Lindsey E Padgett1, Brian Anderson1, Chao Liu2

  • 1Department of Microbiology, Comprehensive Diabetes Center, University of Alabama at Birmingham School of Medicine, Birmingham, AL.

Diabetes
|August 14, 2015
PubMed

Insights

Superoxide, generated by NADPH oxidase (NOX) in CD4 T cells, normally controls autoimmune responses. Its deficiency in mice leads to increased T1D risk by impairing regulatory T cell function.

Area of Science:

  • Immunology
  • Cell Biology
  • Endocrinology

Background:

  • Reactive oxygen species (ROS), particularly superoxide, are crucial in biological systems.
  • CD4 T cells, in addition to immune cells like neutrophils and macrophages, express NADPH oxidase (NOX), an enzyme that generates superoxide.
  • Previous studies showed that superoxide-deficient mice (NOD.Ncf1(m1J)) had delayed type 1 diabetes (T1D) linked to reduced IFN-γ by CD4 T cells.

Purpose of the Study:

  • To investigate the role of superoxide in CD4 T-cell-mediated diabetogenicity.
  • To explore how superoxide deficiency impacts T1D development and CD4 T-cell function.
  • To elucidate the mechanisms by which superoxide influences T-cell responses and regulatory T cells (Tregs).

Main Methods:

  • Generation and analysis of a novel mouse strain (NOD.BDC-2.5.Ncf1(m1J)) with autoreactive CD4 T cells deficient in NOX-derived superoxide.
  • Assessment of Th1 cytokine and chemokine synthesis in stimulated CD4 T cells and splenocytes.
  • Evaluation of T1D development in superoxide-deficient mice and adoptive transfer experiments.
  • Analysis of Treg suppression, IL-12Rβ2 signaling, and P-STAT4 activation.

Main Results:

  • Superoxide-deficient BDC-2.5 mice developed spontaneous T1D.
  • CD4 T cells from these mice were more diabetogenic, associated with impaired Treg suppression.
  • Exogenous superoxide normalized exacerbated Th1 cytokines and chemokines, reduced IL-12Rβ2 signaling, and P-STAT4 activation.

Conclusions:

  • NOX-derived superoxide is critical for suppressing autoreactivity in CD4 T cells.
  • Superoxide controls Treg function and acts as a redox-dependent checkpoint for effector T-cell responses.
  • Free radicals, specifically superoxide, play a complex role in regulating CD4 T-cell responses and autoimmunity.

More Related Videos

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes12:12

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes

Published on: June 16, 2011

14.1K
Bioluminescent Monitoring of Graft Survival in an Adoptive Transfer Model of Autoimmune Diabetes in Mice10:03

Bioluminescent Monitoring of Graft Survival in an Adoptive Transfer Model of Autoimmune Diabetes in Mice

Published on: November 18, 2022

2.4K

Related Concept Videos

Diabetes Mellitus: Overview and Type I Subtype01:22

Diabetes Mellitus: Overview and Type I Subtype

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
6.1K
Carbohydrate Metabolism01:36

Carbohydrate Metabolism

Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
15.0K
Diabetes Mellitus: Type 2 and Gestational01:22

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
5.6K
Pathophysiology of Diabetes01:20

Pathophysiology of Diabetes

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
4.5K
Psychoneuroimmunology: Diabetes and Cancer01:19

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
634
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.3K