Mononucleated blood cell populations display different abilities to transmit prion disease by the transfusion route

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Douet, Jean-Yves | Lacroux, Caroline, C. | Litaise, Claire | Lugan, Séverine, S. | Corbière, Fabien | Arnold, Mark | Simmons, Hugh | Aron, Naima, N. | Costes, Pierrette, P. | Tillier, Cecile | Cassard, Hervé, H. | Andréoletti, Olivier

Edité par CCSD ; American Society for Microbiology -

International audience. Previous experiments carried out in a sheep scrapie model demonstrated that the transfusion of 200 mu l of prion-infected whole blood has an apparent 100% efficacy for disease transmission. These experiments also indicated that, despite the apparent low infectious titer, the intravenous administration of white blood cells (WBC) resulted in efficient disease transmission. In the study presented here, using the same transmissible spongiform encephalopathy (TSE) animal model, our aim was to determine the minimal number of white blood cells and the specific abilities of mononucleated cell populations to transmit scrapie by the transfusion route. Our results confirmed that the transfusion of 100 mu l, but not 10 mu l, of fresh whole blood collected in asymptomatic scrapie-infected donor sheep can transmit the disease. The data also show that the intravenous administration of 105 WBCs is sufficient to cause scrapie in recipient sheep. Cell-sorted CD45R(+) (predominantly B lymphocytes), CD4(+)/CD8(+) (T lymphocytes), and CD14(+) (monocytes/macrophages) blood cell subpopulations all were shown to contain prion infectivity by bioassays in ovine PrP transgenic mice. However, while the intravenous administration of 106 CD45(+) or CD4(+)/8(+) living cells was able to transmit the disease, similar numbers of CD14(+) cells failed to infect the recipients. These data support the contention that mononucleated blood cell populations display different abilities to transmit TSE by the transfusion route. They also represent an important input for the risk assessment of blood-borne prion disease transmission and for refining the target performance of leukoreduction processes that currently are applied to mitigate the transmission risk in transfusion medicine.

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