Follicular dendritic cells in scrapie pathogenesis.
Scrapie pathogenesis was studied in chimaeric mice that carried the prion protein (PrP) gene only in particular cells of the immune system. These mice were produced by grafting bone marrow from PrP expressing donors into PrP deficient recipients and vice versa. As follicular dendritic cells are not replaced significantly from the bone marrow in adult mice, this procedure resulted in a mismatch in PrP genotype between these cells and bone marrow derived cells such as lymphocytes. Using these models we obtained strong evidence that follicular dendritic cells produced high levels of the normal form of PrP in uninfected mice. Furthermore, the replication of a mouse-passaged scrapie strain in the spleen depended only on the presence of PrP expressing follicular dendritic cells. PrP expression by lymphocytes or other bone marrow derived cells had no influence on replication in spleen or on neuroinvasion in these models. These results indicate that the follicular dendritic cell is a potential target for prophylactic or therapeutic intervention in transmissible spongiform encephalopathies.
Brown
K L
KL
Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, UK.
Stewart
K
K
Ritchie
D
D
Fraser
H
H
Morrison
W I
WI
Bruce
M E
ME
D000818:Animals; D020566:Dendritic Cells, Follicular / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D018620:PrPSc Proteins / Q000235:genetics* / Q000378:metabolism*; D012608:Scrapie / Q000503:physiopathology*
D018620:PrPSc Proteins