Table of Contents Author Guidelines Submit a Manuscript
Developmental Immunology
Volume 8, Issue 3-4, Pages 291-304
http://dx.doi.org/10.1155/2001/95404

Studies on Prion Replication in Spleen

1lnstitute of Neuropathology, University Hospital, Zürich 8091, Switzerland
2lnstitute of Molecular Biology, University of Zürich, Zürich 8057, Switzerland
3Cytos Biotechnology AG, Wagistr. 21, Zürich-Schlieren 8952, Switzerland
4MRC Prion Unit/Neurogenetics, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK

Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Some of the early events following scrapie infection take place in the lymphoreticular system (LRS) and result in significant replication of prions in lymphoid organs. The identity of the cells in the LRS that produce prions and their role in neuroinvasion are still unknown. We find that in the spleen of scrapie-infected mice, prions are associated with T and B cells and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDC's); curiously, no infectivity was found in lymphocytes from blood of the same mice. Thus, splenic lymphocytes either replicate prions or acquire them from another source. Studies on PrP knockout mice with ectopic expression of PrP restricted to only B or T lymphocytes suggest that neither of these by themselves are competent for prion replication. To determine whether B and T cells are able to pick up prions from other sources, irradiated wild-type mice were reconstituted with PrP-deficient lymphohaematopoietic stem cells. Following intraperitoneal inoculation of these mice, no infectivity was found on splenic lymphocytes whereas the stroma (comprising the radiation-resistant, PrP-expressing FDC's) contained prions. These results imply that splenic lymphocytes can acquire prions, possibly from FDC's, but only if they express PrP.