Delgado Ana Lledo, Preston-Hurlburt Paula, Lim Noha, Sumida Tomokazu S, Long S Alice, McNamara James, Serti Elisavet, Higdon Lauren, Herold Kevan C
medRxiv. 2023 Jul 13:2023.07.11.23292344. doi: 10.1101/2023.07.11.23292344.
Teplizumab has been approved for the delay of the onset of type 1 diabetes and may modulate new onset disease. We found that patients who were EBV positive at baseline had a more robust response to drug in two clinical trials and therefore postulated that latent virus has general effects in modifying immune responses. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and partially exhausted CD8 T cells were found in EBV seropositive individuals at the baseline in the TN10 trial and AbATE trial. Single cell transcriptomics and functional assays identified downregulation of the T cell receptor and other signaling pathways before treatment. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways generally in immune cells, that broadly redirect cell differentiation.
替普珠单抗已被批准用于延缓1型糖尿病的发病，并可能调节新发病例。我们发现在两项临床试验中，基线时EBV呈阳性的患者对药物的反应更强，因此推测潜伏病毒在改变免疫反应方面具有普遍作用。我们比较了替普珠单抗治疗前后外周血细胞的表型、转录组和发育情况。在TN10试验和AbATE试验中，基线时EBV血清阳性个体中发现了更多的调节性T细胞和部分耗竭的CD8 T细胞。单细胞转录组学和功能分析确定了治疗前T细胞受体和其他信号通路的下调。替普珠单抗治疗增强了EBV血清阳性个体中适应性免疫细胞功能的损伤。我们的数据表明，EBV通常会损害免疫细胞中的信号通路，从而广泛地重新引导细胞分化。
