IMMUNE SYSTEM-DEPENDENT AND SYSTEM-INDEPENDENT REPLICATION OF THE SCRAPIE AGENT

Using the severe combined immunodeficiency (SCID) mouse model, we inve stigated the requirement of the immune system for the development of s crapie after peripheral inoculation. A total of 33% of SCID mice, all but one immunologically reconstituted SCID mice (93%), and all CB17 co ntrol mice developed the disease. PrPres was detectable in the brains of all diseased animals and in the spleens of reconstituted SCID and C B17 control mice but not of the diseased non-immunologically reconstit uted SCID mice. The immune system appears to be a primary target in th e pathogenesis of scrapie, but direct spread to the central nervous sy stem from the peritoneum via visceral nerve fibers can probably also o ccur.