Decreased GAD(65)-specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum

Diabetic Medicine : a Journal of the British Diabetic Association
S AxelssonRosaura Casas

Abstract

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 Type 1 diabetes, focusing on chemokines and their receptors. Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. 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. 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 GAD(65) immunity.

References

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Citations

Jul 28, 2013·Current Diabetes Reports·Leonard C HarrisonGrant Morahan
Jan 1, 2012·The Review of Diabetic Studies : RDS·Ken T CoppietersMatthias G von Herrath
Mar 16, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Ken T CoppietersMatthias G von Herrath
Oct 30, 2013·Human Vaccines & Immunotherapeutics·Anna K E RydénMatthias G Von Herrath

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