Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes

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 (GAD(65)), 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.