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Prions and the lymphoreticular system.

C Weissmann1, A J Raeber, F Montrasio

  • 1Medical Research Council Prion Unit, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK. c.weissmann@ic.ac.uk

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|March 22, 2001
PubMed
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Scrapie prion infectivity initially targets the spleen, associating with lymphocytes and follicular dendritic cells (FDCs). Blocking FDC development halts prion accumulation and slows brain invasion, highlighting FDCs

Area of Science:

  • Neuroscience
  • Immunology
  • Prion Biology

Background:

  • Scrapie prions, infectious agents causing neurodegenerative diseases, initially accumulate in the spleen before affecting the brain.
  • Understanding prion tropism and replication sites is crucial for developing therapeutic strategies against prion diseases.

Purpose of the Study:

  • To investigate the cellular reservoirs and replication mechanisms of scrapie prions within the spleen.
  • To elucidate the role of specific immune cells and stromal components, particularly follicular dendritic cells (FDCs), in prion propagation and neuroinvasion.

Main Methods:

  • Inoculation of mice with scrapie prions via intracerebral or peripheral routes.
  • Analysis of prion distribution in spleen and blood lymphocytes using transgenic mice expressing PrP in T or B cells.

Related Experiment Videos

  • Treatment with soluble lymphotoxin-beta receptor to deplete mature FDCs and assess the impact on prion accumulation and neuroinvasion.
  • Main Results:

    • Scrapie infectivity was primarily found in splenic T and B lymphocytes and associated with follicular dendritic cells (FDCs), but not in blood lymphocytes.
    • Transgenic mice lacking PrP expression in lymphocytes showed no prion replication in the lymphoreticular system.
    • Depletion of FDCs by soluble lymphotoxin-beta receptor treatment abolished splenic prion accumulation and significantly retarded neuroinvasion.

    Conclusions:

    • Splenic lymphocytes are involved in prion accumulation, but their replication likely depends on other PrP-expressing cells, notably FDCs.
    • Follicular dendritic cells (FDCs) play an essential role in splenic prion replication and are critical for efficient neuroinvasion.
    • Targeting FDCs represents a potential therapeutic strategy to control prion spread and disease progression.