Resistance to the induction of EAE in AO rats: Its prevention by the pre-treatment with cyclophosphamide or low dose of irradiation

Abstract

Susceptibility to the induction of EAE was compared in AO, DA and Lewis strain of rats. As evaluated by clinical and histological criteria, AO rats exhibited significantly lower susceptibility to EAE induced with guinea-pig spinal cord (GPSC) tissue and complete resistance to the encephalitogenic challenge with rat myelin basic protein (BP) irrespective of antigen dose and adjuvant used. AO rats pre-treated with BP + Freund's incomplete adjuvant became completely unresponsive to the induction of EAE with GPSC + Freund's complete adjuvant (FCA) indicating that they do possess cells sensitive to some antigenic determinants of rat BP. In order to test whether the resistance to EAE is due to an active suppression, low dose of irradiation (300 rad) and cyclophosphamide (20 mg/kg) was applied prior to the induction of EAE. Selective depletion of radiosensitive cells facilitated the induction of EAE. Similarly, cyclosphosphamide given 2 days prior to BP + FCA completly abrogated the resistance to EAE induction. Thus, it appears that the inability of BP + FCA to produce EAE in AO rats is due to the disproportionate activation of suppressor cells.