Immuocytochemical and ultrastructural studies of lymphoid tissue of scrapie infected mice and sheep

The transmissible spongiform encephalopathies (TSEs) are a group of progressive neurological diseases of unknown cause. Infection is associated with an abnormal form of a host protein designated 'prion protein'. Previous studies have shown that lymphoid tissues are involved in the peripheral pathogenesis of TSEs prior to neuroinvasion. Using immunoelectron microscopy, disease specific PrP (PrPd) accumulation was demonstrated within the spleens of scrapie-infected mice where it was found in association with the plasmalemma and extracellular space around follicular dendritic cell (FDC) processes (dendrites), and in the lysosomes of tingible body macrophages (TBMs). In light zones of secondary follicles, almost all FDCs at the terminal stages of disease form hypertrophic labyrinthine glomerular complexes. Within these labyrinthine complexes PrPd is consistently seen on the plasmalemma of adjacent dendritic profiles and in association with abundant electron dense material held between dendrites. The latter was interpreted as excess trapped antigenantibody complexes. Contrary to previous dogma, these results show that a pathological response within the immune system follows murine scrapie infection. The nature of these changes is similar irrespective of the strain of agent used. To help determine the significance of these changes, scrapie-infected mice were inoculated with cytokines that alter the biology of secondary follicles. Tumour necrosis factor receptor fusion protein (Hu-TNFR:Fc) or Lymphotoxin P receptor fusion protein (LTPR:Fc), have been reported to induce de-differentiation of FDCs and heighten B cell apoptosis. However, in this study, mature FDCs were present 3 and 35 days after treatment with LTpR:Fc and retained PrPd accumulation. The mechanisms by which these cytokines modulate incubation period were not determined. To ensure that the pathology of experimental disease is similar to that occurring in natural disease, ovine scrapie tissue samples were examined. The results presented suggest that natural scrapie is closely similar to that of experimental murine scrapie. Further technique refinement is still necessary to give comparable levels of sensitivity and tissue preservation in ovine tissue