title: Decreased GAD(65)-specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Paediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. stina.axelsson@liu.se
authors.forename: S
authors.initials: S
authors.lastname: Axelsson
authors.forename: M
authors.initials: M
authors.lastname: Hjorth
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: R
authors.initials: R
authors.lastname: Casas
mesh_terms: D000293:Adolescent; D000536:Aluminum Hydroxide / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005968:Glutamate Decarboxylase / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010641:Phenotype; D054398:Receptors, CCR4 / Q000187:drug effects; D019713:Receptors, CCR5 / Q000187:drug effects; D013548:Sweden; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects*
chemical_list: D054398:Receptors, CCR4; D019713:Receptors, CCR5; D000536:Aluminum Hydroxide; D005968:Glutamate Decarboxylase