Prions and the lymphoreticular system

Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie-infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, w...

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Veröffentlicht in:Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2001-02, Vol.356 (1406), p.177-184
Hauptverfasser: Dobson, C. M., Ellis, R. J., Fersht, A. R., Weissmann, Charles, Raeber, Alex J., Montrasio, Fabio, Hegyi, Ivan, Frigg, Rico, Klein, Michael A., Aguzzi, Adriano
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container_issue 1406
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container_title Philosophical transactions of the Royal Society of London. Series B. Biological sciences
container_volume 356
creator Dobson, C. M.
Ellis, R. J.
Fersht, A. R.
Weissmann, Charles
Raeber, Alex J.
Montrasio, Fabio
Hegyi, Ivan
Frigg, Rico
Klein, Michael A.
Aguzzi, Adriano
description Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie-infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDCs) but not with non-B, non-T cells; strikingly, no infectivity was found in lymphocytes from blood of the same mice. Transgenic PrP knockout mice expressing PrP restricted to either B or T lymphocytes show no prion replication in the lymphoreticular system. Therefore, splenic lymphocytes either acquire prions from another source or replicate them in dependency on other PrP-expressing cells. The essential role of FDCs in prion replication in spleen was shown by treating mice with soluble lymphotoxin-β receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion following intraperitoneal scrapie inoculation.
doi_str_mv 10.1098/rstb.2000.0763
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source Jstor Complete Legacy; MEDLINE; PubMed Central
subjects Animals
B Lymphocytes
Central nervous system
Creutzfeldt Jakob syndrome
Dendritic Cells
Ectopic Expression
Follicular Dendritic Cells
Humans
Infections
Inoculation
Lymphatic System - physiology
Lymphocytes
Lymphotoxin
Mice
Mice, Knockout
Mononuclear Phagocyte System - physiology
Peptide Fragments - genetics
Prion diseases
Prions
Prions - genetics
Prions - metabolism
PrP
Spleen
Spleen - metabolism
T lymphocytes
title Prions and the lymphoreticular system
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