Prions and the lymphoreticular system

Following intracerebral or peripheral inoculation of mice with scrapie prio ns, 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 hich 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 e ither B or T lymphocytes show no prion replication in the lymphoreticular s ystem. Therefore, splenic lymphocytes either acquire prions from another so urce or replicate them in dependency on other PrP-expressing cells. The ess ential role of FDCs in prion replication in spleen was shown by treating mi ce with soluble lymphotoxin-beta receptor, which led to disappearance of ma ture FDCs from the spleen and concomitantly abolished splenic prion accumul ation and retarded neuroinvasion following intraperitoneal scrapie inoculat ion.