Combination of worm antigen and proinsulin prevents type 1 diabetes in NOD mice after the onset of insulitis

Clin Immunol. 2016 Mar:164:119-22. doi: 10.1016/j.clim.2016.02.005. Epub 2016 Feb 16.

Abstract

Animal studies demonstrated that administration of helminth products can protect from autoimmune diseases. However, the success of such administrations is limited in the case of type 1 diabetes, as protection is only provided if the administration is started before the development of insulitis. In this study we investigated whether inclusion of helminth antigen administrations to an antigen-specific treatment with proinsulin improves the protective effect by triggering non-specific regulatory immune responses. Using a combination therapy of intraperitoneal Litomosoides sigmodontis antigen and intranasal pro-insulin, onset of diabetes was prevented in NOD mice after insulitis started, while either administration alone failed to protect. This protection was associated with an increased frequency of regulatory T cells within the pancreatic lymph nodes and a reduced inflammation of the pancreatic islets. This suggests that inclusion of helminth antigens improve the protective effect provided by antigen-specific therapies and represent a new potential therapeutic approach against autoimmune diseases.

Keywords: Filariae; Helminth; Litomosoides sigmodontis; Proinsulin; Regulatory T cells; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antigens, Helminth / pharmacology
  • Antigens, Helminth / therapeutic use*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Filarioidea / immunology*
  • Injections, Intraperitoneal
  • Insulin / immunology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / immunology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mice, Inbred NOD
  • Proinsulin / pharmacology
  • Proinsulin / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antigens, Helminth
  • Insulin
  • Proinsulin