We previously reported that mice intracerebrally inoculated with the mouse-adapted scrapie strain ME7 have markedly diminished T zones in the spleen due to the decreased expression of CCL19 and CCL21. In addition, follicular dendritic cell networks in germinal centers were larger in ME7-infected spleens compared to uninfected spleens. As an extension of that study, we set out to determine how ME7 infection affects spleen structure and follicular helper T (Tfh) cell responses in mice. For this study, mice were intraperitoneally inoculated with brain homogenate of the ME7 inoculum and spleens were analyzed 50, 130, and 200 days after inoculation and compared with those from uninfected mice. The result showed that ME7- infected mice had increased Tfh cell responses which were maintained until end-stage prion disease. Although CD4 T cells decreased in white pulps, they increased in germinal centers, and expressed higher levels of the Tfh-related genes, such as Bcl6, Il21, Cxcr5, Icos, and Pdcd1. In addition, ME7-infected spleens had increased numbers of CD4 memory T cells. These data indicate that although ME7 infection led to impaired splenic white pulp structure, CD4 memory T cells were increased and Tfh cell responses were required and prolonged to provide help for the replication and accumulation of pathogenic prion protein in germinal centers.

我们之前曾报道过，由于CCL19和CCL21的表达降低，用小鼠适应的瘙痒病ME7脑内接种的小鼠脾脏中的T区明显减少。另外，与未感染的脾相比，在ME7感染的脾中生发中心的滤泡树突状细胞网络更大。作为该研究的延伸，我们着手确定ME7感染如何影响小鼠的脾脏结构和滤泡辅助性T（Tfh）细胞反应。在这项研究中，小鼠腹膜内接种了ME7接种物的脑匀浆，并在接种后50、130和200天对脾进行了分析，并与未感染小鼠进行了比较。结果表明，感染ME7的小鼠具有增加的Tfh细胞反应，这种反应一直持续到晚期stage病毒病。Bcl6，Il21，Cxcr5，Icos和Pdcd1。另外，感染ME7的脾脏具有增加的CD4记忆T细胞数量。这些数据表明，尽管ME7感染导致脾脏白髓结构受损，但CD4记忆T细胞增加，需要Tfh细胞反应并延长反应时间，以帮助致病性ion病毒蛋白在生发中心的复制和积累。