Detection of PrP Sc in Lymphoid Tissues of Lambs Experimentally Exposed to the Scrapie Agent

Histoblotting and immunohistochemistry were used to detect disease-associated prion protein (PrP Sc) in lymphoid tissues of lambs of known PrP genotype infected with the scrapie agent by stomach tube at the age of 2 months. The ileal and jejunal Peyer's patches and retropharyngeal and distal jejunal lymph nodes were studied 1 week, 5 weeks, 5 months and 11 months after inoculation. Other lymphoid tissues examined included superficial cervical lymph node, tonsil and spleen. PrP Sc was not detected in any tissue of any lamb at 1 week post-inoculation. At 5 weeks, PrP Sc was detected in tissues of lambs of susceptible PrP genotypes (AV 136QQ 171 and VV 136QQ 171), but not lambs of other PrP genotypes (AA 136QQ 171, AA 136QR 171 and AV 136QR 171). PrP Sc was present in the germinal centres of tonsils, distal jejunal and retropharyngeal lymph nodes, and spleen. In the nodules of ileal and jejunal Peyer's patches, only occasional solitary cells showed the presence of PrP Sc. At 5 months post-inoculation, increased accumulations of PrP Sc were detected in ileal and jejunal Peyer's patches, as well as in the retropharyngeal and distal jejunal lymph nodes of a single lamb inoculated with the agent from a sheep of the same susceptible PrP genotype. Eleven months after exposure to the scrapie agent, PrP Sc was detected in all lymphoid tissues examined from sheep of susceptible PrP genotypes. These studies show that PrP Sc was detectable in lymphoid tissues 5 weeks after exposure to the scrapie agent by stomach tube in lambs as young as 3 months of age and indicate that the PrP genotype is a significant factor for the rapid uptake and spread of the agent through lymphoid tissues.