Detection of PrP in extraneural tissues

Transmissible spongiform encephalopathies (TSEs) or "prion diseases" are a group of unconventional fatal diseases. TSEs are characterised by the accum ulation of a modified form of the normal host glycoprotein, PrP (PrPc). In the course of infection PrPc is converted to an abnormally protease resista nt form, PrPSc. The exact nature of the infectious agent responsible for th ese diseases remains controversial. While there is compelling evidence that TSE agents contain an informational molecule, possibly a nucleic acid, som e believe that the infectious agent or "prion" is solely composed of PrPSc. Nevertheless, PrP is required for TSE pathogenesis, as mice devoid of the PrP gene (PrP-/-) remain healthy when challenged with TSE isolates and are unable to replicate infectivity within the central nervous system (CNS) or in other tissues. In recent years immunocytochemistry has been used to pinp oint which cells are associated with abnormal accumulations of PrP, providi ng important information on the cellular targeting of TSE infection. In uni nfected and scrapie-infected mice, PrP protein is found in the CNS and in e xtraneural tissues such as spleen and lymph nodes. In the peripheral lympho id system, PrP is associated with follicular dendritic cells that are known to be important for replication of infectivity for at least one TSE strain . This review will focus on current methods for the immunocytochemical dete ction of PrP in murine extraneural tissues, mainly lymphoid tissues, and wi ll discuss recent findings on the role of the peripheral lymphoid system in TSE pathogenesis. (C) 2000 Wiley-Liss. Inc.