Decreased GAD65-specific Th1/Tc1 phenotype in children with Type1 diabetes treated with GAD-alum

Abstract

Aim The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type1 diabetes, focusing on chemokines and their receptors. Methods Blood samples were collected from 70 children with Type1 diabetes included in a phaseII clinical trial with GAD-alum. Expression of CC chemokine receptor5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD65 using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD65 immunity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.