Detection of PrP in extraneural tissues

Abstract

Transmissible spongiform encephalopathies (TSEs) or "prion diseases" are a group of unconventional fatal diseases. TSEs are characterised by the accumulation of a modified form of the normal host glycoprotein, PrP (PrP(c)). In the course of infection PrP(c) is converted to an abnormally protease resistant form, PrP(Sc). The exact nature of the infectious agent responsible for these diseases remains controversial. While there is compelling evidence that TSE agents contain an informational molecule, possibly a nucleic acid, some believe that the infectious agent or "prion" is solely composed of PrP(Sc). 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 pinpoint which cells are associated with abnormal accumulations of PrP, providing important information on the cellular targeting of TSE infection. In uninfected and scrapie-infected mice, PrP protein is found in the CNS and in extraneural tissues such as spleen and lymph nodes. In the peripheral lymphoid 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 detection of PrP in murine extraneural tissues, mainly lymphoid tissues, and will discuss recent findings on the role of the peripheral lymphoid system in TSE pathogenesis.