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Studies on prion replication in spleen.

A J Raeber1, F Montrasio, I Hegyi

  • 1Institute of Neuropathology, University Hospital, Zürich, Switzerland. raeber@cytos.com

Developmental Immunology
|January 12, 2002
PubMed
Summary
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Scrapie infection involves prions in the spleen, associated with T and B cells. Lymphocytes acquire prions from follicular dendritic cells, but only if they express PrP.

Area of Science:

  • Neuroscience
  • Immunology
  • Prion Biology

Background:

  • Scrapie infection initially affects the lymphoreticular system (LRS), leading to prion replication in lymphoid organs.
  • The specific LRS cells responsible for prion production and their role in neuroinvasion remain unclear.

Purpose of the Study:

  • To identify the cells within the LRS involved in prion replication and their contribution to neuroinvasion.
  • To investigate the mechanism by which splenic lymphocytes interact with prions during scrapie infection.

Main Methods:

  • Analysis of prion association with splenic T cells, B cells, and stromal components (including follicular dendritic cells) in scrapie-infected mice.
  • Studies using PrP knockout mice with targeted PrP expression in B or T lymphocytes.
  • Experiments involving reconstitution of irradiated wild-type mice with PrP-deficient lymphohaematopoietic stem cells followed by prion inoculation.

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Main Results:

  • Prions were found associated with splenic T and B cells, and to a lesser extent, with follicular dendritic cells (FDCs) in scrapie-infected mice.
  • Lymphocytes from the blood of infected mice showed no infectivity, suggesting splenic lymphocytes either replicate or acquire prions.
  • Neither B nor T lymphocytes alone were competent for prion replication.
  • Splenic lymphocytes acquired prions from FDCs, but only when the lymphocytes expressed PrP.

Conclusions:

  • Splenic lymphocytes can acquire prions, likely from FDCs, but this process is dependent on PrP expression in the lymphocytes.
  • The findings shed light on the cellular dynamics of prion propagation within the lymphoreticular system and its potential link to neuroinvasion.