Pathogenesis of scrapie in ARQ/ARQ sheep after subcutaneous infection: effect of lymphadenectomy and immune cell subset changes in relation to prion protein accumulation.

Although it is well established that the infectious agent can replicate in the lymphoreticular system (LRS) early after inoculation, the information on pathways or cells involved in the dissemination of scrapie from the point of inoculation is limited. In order to gain a better understanding on these mechanisms 16 ARQ/ARQ, polymorphic or non polymorphic Suffolk or Romney lambs were inoculated subcutaneously with a Suffolk scrapie brain homogenate in the drainage area of the prefemoral lymph node. Fourteen lambs were then either subjected to early or late surgical removal of the prefemoral lymph nodes or not subjected to lymphadectomy and used as positive controls. Eleven animals were culled at a preclinical stage of the disease, and only 5, including 2 positive controls, were killed after reaching clinical end point. Of 5 polymorphic animals killed at preclinical stages of infection, two did not show any evidence of infection, two showed little involvement of LRS tissues and little or none in brain, and one showed widespread LRS involvement but mild PrPd accumulation in the CNS. This was in contrast with the findings in non-polymorphic sheep which, at comparable dpi, showed a complete attack rate with widespread PrPd accumulation in LRS tissues and many of them also in the CNS. The only polymorphic sheep left to develop clinical signs reached enpoint with a more protracted incubation period than the non-polymorphic sheep, but with similar PrPd magnitudes in the LRS or brain. The only change that appears to be related to PrPd accumulation in the LNs is the increase in CD21+ cells indistinctly in polymorphic or polymorphic animals.