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The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c<jats:sup>+<\/jats:sup>lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-\u03b1) and LT-\u03b2 signaling components. We report here that by the oral route, LT-\u03b1 \u2212\/\u2212 mice developed scrapie while LT-\u03b2 \u2212\/\u2212 mice did not. Furthermore, LT-\u03b1 \u2212\/\u2212 mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-\u03b2 \u2212\/\u2212 mice. Transplantation of lymphoid tissues from LT-\u03b2 \u2212\/\u2212 mice, which have cervical and mesenteric lymph nodes, into LT-\u03b1 \u2212\/\u2212 mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c<jats:sup>+<\/jats:sup>cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c<jats:sup>+<\/jats:sup>cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-\u03b1 \u2212\/\u2212 than in LT-\u03b2 \u2212\/\u2212 mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.<\/jats:p>","DOI":"10.1128\/jvi.76.9.4357-4363.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:59:40Z","timestamp":1027763980000},"page":"4357-4363","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Lymphotoxin-\u03b1- and Lymphotoxin-\u03b2-Deficient Mice Differ in Susceptibility to Scrapie: Evidence against Dendritic Cell Involvement in Neuroinvasion"],"prefix":"10.1128","volume":"76","author":[{"given":"Michael B. 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