Antigen-specific demyelination and significance of the bystander effect in peripheral nerves

In an experiment designed to evaluate bystander demyelination in peripheral nerve, immune reactions to tuberculin and albumin failed to induce demyelination, except in animals previously sensitized to a myelin component. The peripheral nerves of tuberculin-sensitized rats and guinea pigs and rabbits were examined at intervals from 8 to 144 hours after intraneural challenge with purified protein derivative (PPD). The results were compared with the immune reaction produced by endoneurial injection of bovine serum albumin (BSA) in rats sensitized to BSA in Freund's complete antigen (FCA). Tuberculin-sensitized rats responded to endoneurial PPD injection by developing perivascular lymphocytic infiltrates which were most severe 5 days after injection. Albumin-sensitized rats responded within hours of BSA injection, showing severe endoneurial edema due to vasculitis with extravasation of polymorphonuclear leukocytes, red cells, and fibrin. The reaction tapered off within 2 days. No significant demyelination occurred in either group. However, demyelination was elicited when the hapten galactocerebroside (GC) was included in the sensitizing inoculum. Schwann-cell necrosis was visible 2 days after endoneurial challenge injection, and demyelination became extensive 5 days after injection. The findings were compared with those after direct injection of anti-GC-antibody, which produced demyelination by lysis of Schwann cells. In rabbits the occurrence of demyelination correlated with the presence of circulating antibodies to GC.