Zander Ryan A, Vijay Rahul, Pack Angela D, Guthmiller Jenna J, Graham Amy C, Lindner Scott E, Vaughan Ashley M, Kappe Stefan H I, Butler Noah S
Cell Rep. 2018 Apr 24;23(4):1230-1237. doi: 10.1016/j.celrep.2018.04.048.
Effector T-cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental infection and are believed to be critical for resistance to clinical malaria. To determine whether -specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T-cells in experimental models. We found that populations of both Th1- and Tfh-like -specific memory CD4 T-cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B-cell help and protection following transfer, characteristics that are enhanced following ligation of the T-cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of -specific memory CD4 T-cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against parasite re-exposure.
表现出T辅助细胞1（Th1）或滤泡辅助性T细胞（Tfh）群体特征的效应T细胞对于控制实验性感染至关重要，并且被认为对抵抗临床疟疾至关重要。为了确定特异性的Th1和Tfh样效应细胞是否产生有助于保护的记忆群体，我们开发了转基因寄生虫，以便在实验模型中对抗疟疾记忆CD4 T细胞进行高分辨率研究。我们发现Th1和Tfh样特异性记忆CD4 T细胞群体都持续存在。出乎意料的是，Th1样记忆细胞在回忆过程中表现出Tfh细胞的表型和功能特征，并在转移后提供强大的B细胞帮助和保护，在T细胞共刺激受体OX40连接后这些特征会增强。我们的研究结果描绘了特异性记忆CD4 T细胞的关键功能属性，并确定了一个宿主特异性因子，该因子可作为靶点来提高急性疟疾的治愈率，并提供针对寄生虫再次暴露的持久长期保护。
