Inhibition of experimental autoimmune neuritis by an antibody to the lymphocyte function-associated antigen-1

Lab Invest. 1994 May;70(5):667-75.

Abstract

Background: Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome. The mechanisms underlying cellular trafficking and homing of autoreactive immune cells to the peripheral nervous system during EAN and Guillain-Barré syndrome are unknown. We investigated the role of the adhesion molecule lymphocyte function-associated antigen-1 in the pathogenesis of EAN.

Experimental design: EAN was induced in Lewis rats either by immunization with bovine spinal root myelin or by adoptive transfer of P2-specific T cells. Animals were treated intraperitoneally with a monoclonal antibody to lymphocyte function-associated antigen-1 (WT-1) or phosphate-buffered saline and scored for clinical signs. Histology was performed on sciatic nerve and cauda equina and assessed for infiltration and demyelination. Severity of EAN and the corresponding histologic alterations were compared in the different treatment groups. The in vitro effect of WT-1 on T cell proliferation was evaluated.

Results: Treatment with WT-1 prevented or efficiently suppressed myelin-induced EAN. In contrast, sham treatment of animals failed to alter the clinical course of EAN. Histologic examination of the peripheral nervous system showed a marked reduction of inflammatory infiltration and perivascular demyelination in animals treated with WT-1. Adoptive transfer EAN was not affected by the administration of WT-1. The differential action in the two models suggests that WT-1 appears to act primarily on the induction phase of the immune response but has no significant impact on the effector phase. In vitro studies with WT-1 revealed that the antibody inhibits the concanavalin A-dependent proliferation of neuritogenic P2-specific T cells.

Conclusions: Our data indicate that lymphocyte function-associated antigen-1 is critically involved in the pathogenesis of EAN. Further analysis of this model may provide insight into the process of immune cell recruitment from the circulation into the peripheral nervous system in immune-mediated neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Cattle
  • Female
  • Flow Cytometry
  • Immunization
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation*
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Myelin Sheath / immunology
  • Neuritis, Autoimmune, Experimental / immunology
  • Neuritis, Autoimmune, Experimental / pathology
  • Neuritis, Autoimmune, Experimental / prevention & control*
  • Polyradiculoneuropathy / immunology
  • Rats
  • Rats, Inbred Lew
  • Spinal Nerve Roots / immunology
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Lymphocyte Function-Associated Antigen-1