INHIBITION OF EXPERIMENTAL AUTOIMMUNE NEURITIS BY AN ANTIBODY TO THE LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1

BACKGROUND: Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barre syndrome. The mechanisms underlying cellular traffic king and homing of autoreactive immune cells to the peripheral nervous system during EAN and Guillain-Barre syndrome are unknown. We investi gated the role of the adhesion molecule lymphocyte function-associated antigen-1 in the pathogenesis of EAN. EXPERIMENTAL DESIGN: EAN was in duced in Lewis rats either by immunization with bovine spinal root mye lin or by adoptive transfer of P2-specific T cells. Animals were treat ed intraperitoneally with a monoclonal antibody to lymphocyte function -associated antigen-1 (WT-1) or phosphate-buffered saline and scored f or clinical signs. Histology was performed on sciatic nerve and cauda equina and assessed for infiltration and demyelination. Severity of EA N and the corresponding histologic alterations were compared in the di fferent treatment groups. The in vitro effect of WT-1 on T cell prolif eration was evaluated. RESULTS: Treatment with WT-1 prevented or effic iently suppressed myelin-induced EAN. In contrast, sham treatment of a nimals failed to alter the clinical course of EAN. Histologic examinat ion of the peripheral nervous system showed a marked reduction of infl ammatory infiltration and perivascular demyelination in animals treate d with WT-1. Adoptive tranfer EAN was not affected by the administrati on 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 respo nse but has no significant impact on the effector phase. In vitro stud ies with WT-1 revealed that the antibody inhibits the concanavalin A-d ependent proliferation of neuritogenic P2-specific T cells. CONCLUSION S: Our data indicate that lymphocyte function-associated antigen-1 is critically involved in the pathogenesis of EAN. Further analysis of th is model may provide insight into the process of immune cell recruitme nt from the circulation into the peripheral nervous system in immune-m ediated neuropathies.