Antigen-specific immunosuppression: nasal tolerance to P0 protein peptides for the prevention and treatment of experimental autoimmune neuritis in Lewis rats

J Neuroimmunol. 1999 Feb 1;94(1-2):109-21. doi: 10.1016/s0165-5728(98)00232-x.

Abstract

Experimental autoimmune neuritis (EAN) is an autoimmune inflammatory demyelinating disease of the peripheral nervous system (PNS), and represents an animal model of the human Guillain-Barré syndrome (GBS). In this study, we report that nasal administration of the neuritogenic peptide 180-199 and of the cryptic peptide 56-71 of the rat neuritogenic P0 protein of peripheral nerve myelin prevents EAN and attenuates ongoing EAN. Both peptides effectively decreased the severity and shortened clinical EAN. Both a prophylactic and a therapeutic approach proved to be beneficial. These effects were associated with T and B cells hyporesponsiveness to the peptide antigens, reflected by downregulated Th1 cell responses (interferon-gamma secretion) and macrophage function, whereas Th2 cell responses (IL-4 secretion) and transforming growth factor-beta mRNA expression were upregulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cattle
  • Disease Models, Animal
  • Epitopes
  • Gene Expression / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Immunization
  • Immunoglobulin G / immunology
  • Immunosuppression*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymph Nodes / immunology
  • Male
  • Myelin P0 Protein / immunology*
  • Myelin P0 Protein / pharmacology*
  • Neuritis, Autoimmune, Experimental / drug therapy
  • Neuritis, Autoimmune, Experimental / immunology*
  • Neuritis, Autoimmune, Experimental / prevention & control*
  • Peptide Fragments / pharmacology
  • Polyradiculoneuropathy / drug therapy
  • Polyradiculoneuropathy / immunology
  • Polyradiculoneuropathy / prevention & control
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / chemistry
  • Sciatic Nerve / immunology
  • Transforming Growth Factor beta / genetics

Substances

  • Epitopes
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Myelin P0 Protein
  • Peptide Fragments
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-4
  • Interferon-gamma