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l�ll Prions and the lymphoreticular system Weissmann C; Raeber AJ; Montrasio F; Hegyi I; Frigg R; Klein MA; Aguzzi APhilos Trans R Soc Lond B Biol Sci 2001[Feb]; 356 (1406): 177-84Following 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-beta receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion following intraperitoneal scrapie inoculation.|Animals[MESH]|Dendritic Cells[MESH]|Humans[MESH]|Lymphatic System/*physiology[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Mononuclear Phagocyte System/*physiology[MESH]|Peptide Fragments/genetics[MESH]|Prions/genetics/*metabolism[MESH]|Spleen/metabolism[MESH] |