A sensitive immunohistochemical procedure was used to investigate the presence of
prion protein (PrP) in the ileal Peyer's patch of PrP-genotyped lambs, including
scrapie-free lambs and lambs naturally and experimentally exposed to the
scrapie agent. The tyramide signal amplification system was used to enhance the sensitivity of conventional immunohistochemical procedures to show that PrP was widely distributed in the enteric nervous plexus supplying the gut wall. In
scrapie-free lambs, PrP was also detected in scattered cells in the lamina propria and in the dome and interfollicular areas of the Peyer's patch. In the follicles, staining for PrP was mainly confined to the
capsule and cells associated with vascular structures in the light central zone. In lambs naturally exposed to the
scrapie agent, staining was prominent in the dome and neck region of the follicles and was also found to be associated with the follicle-associated epithelium. Similar observations were made in lambs that had received a single oral dose of
scrapie-infected brain material from sheep with a homologous and heterologous PrP genotype 1 and 5 weeks previously. These studies show that the ileal Peyer's patch in young sheep may be an important site of uptake of the
scrapie agent and that the biology of this major gut-associated lymphoid tissue may influence the susceptibility to oral
infection in sheep. Furthermore, these studies suggest that homology or heterology between PrP genotypes or the presence of PrP genotypes seldom associated with disease does not impede uptake of PrP.