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.

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