Weissmann C, Raeber A J, Montrasio F, Hegyi I, Frigg R, Klein M A, Aguzzi A
Medical Research Council Prion Unit, Imperial College School of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK.
Philos Trans R Soc Lond B Biol Sci. 2001 Feb 28;356(1406):177-84. doi: 10.1098/rstb.2000.0763.
Following 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.
在用羊瘙痒病朊病毒对小鼠进行脑内或外周接种后，感染性首先在脾脏中积累，随后才在大脑中积累。在感染羊瘙痒病的小鼠脾脏中，朊病毒与T淋巴细胞和B淋巴细胞相关，与含有滤泡树突状细胞（FDC）的基质的关联程度稍低，但与非B、非T细胞无关；令人惊讶的是，在同一只小鼠血液中的淋巴细胞中未发现感染性。表达仅局限于B淋巴细胞或T淋巴细胞的朊蛋白（PrP）的转基因PrP基因敲除小鼠在淋巴网状系统中未显示朊病毒复制。因此，脾淋巴细胞要么从其他来源获取朊病毒，要么依赖其他表达PrP的细胞进行复制。用可溶性淋巴毒素-β受体处理小鼠，结果显示成熟FDC从脾脏中消失，同时消除了脾脏中朊病毒的积累，并延缓了腹腔接种羊瘙痒病后神经侵袭，这表明FDC在脾脏朊病毒复制中起关键作用。
