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Published on: May 6, 2013
Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes
M G E Karlsson Faresjö1, J Ludvigsson
1Division of Paediatrics and Diabetes Research Centre, Department of Molecular & Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. maria.faresjo@imk.liu.se
Insights
Individuals at high risk for type 1 diabetes, particularly children, show a reduced T-helper 1 cell response to autoantigens. This diminished immune response is linked to beta cell exhaustion, a precursor to diabetes.
Area of Science:
- Immunology
- Endocrinology
- Diabetology
Background:
- T-helper (Th) cells play a critical role in autoimmune diseases like type 1 diabetes.
- The specific profile of Th cells preceding type 1 diabetes onset is not fully understood.
- Understanding Th cell responses in high-risk individuals is crucial for early detection and intervention.
Purpose of the Study:
- To investigate the Th1 and Th2 cell profiles in children and adults at high risk for type 1 diabetes.
- To correlate immune responses with clinical markers of disease progression.
- To elucidate the role of specific autoantigens in triggering immune responses in pre-diabetic individuals.
Main Methods:
- Collected peripheral blood mononuclear cells from high-risk children/adults and healthy controls.
- Utilized the enzyme-linked immunospot (ELISPOT) technique to differentiate Th1 and Th2 lymphocytes.
- Analyzed interferon-gamma (IFN-γ) and interleukin-4 secretion after in vitro stimulation with autoantigens (GAD65, insulin, IA-2).
Main Results:
- High-risk individuals, especially children, exhibited significantly lower IFN-γ secretion upon stimulation with autoantigens compared to healthy controls.
- A diminished Th1-like response was observed in vitro in high-risk children.
- Reduced Th1/Th2 responses correlated with indicators of beta cell exhaustion.
Conclusions:
- A diminished Th1-like immune response to key autoantigens is characteristic of individuals at high risk for type 1 diabetes, particularly children.
- This immune dysregulation may contribute to the pathogenesis of type 1 diabetes by affecting beta cell function.
- Findings suggest potential for immune profiling in early type 1 diabetes risk assessment.
Abstract:
The exact role of T-helper (Th) cells that precede the clinical manifestation of type 1 diabetes remains unclear. The aim of this investigation was to study the Th1- and Th2-like profile in children and adults with high risk of developing the disease. Peripheral blood mononuclear cells were collected from high-risk children and adults and from healthy individuals matched for age and gender. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-gamma (IFN-gamma) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-gamma secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD65), insulin and tyrosinphosphatase (IA-2). Thus, a diminished Th1-like response by in vitro autoantigen stimulation was observed in especially children with a high risk of developing type 1 diabetes. Reduced Th1/Th2 response was related to signs of beta cell exhaustion.
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