da Rosa Larissa C, Scales Hannah E, Benson Robert A, Brewer James M, McInnes Iain B, Garside Paul
School of Infection & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Discov Immunol. 2024 Jan 4;3(1):kyad029. doi: 10.1093/discim/kyad029. eCollection 2024.
Abatacept, a co-stimulatory blocker comprising the extracellular portion of human CTLA-4 linked to the Fc region of IgG1, is approved for the treatment of rheumatoid arthritis. By impairing the interaction between CD28 on T cells and CD80/CD86 on APCs, its mechanisms of action include the suppression of follicular T helper cells (preventing the breach of self-tolerance in B cells), inhibition of cell cycle progression holding T cells in a state described as 'induced naïve' and reduction in DC conditioning. However, less is known about how long these inhibitory effects might last, which is a critical question for therapeutic use in patients. Herein, employing a murine model of OVA-induced DTH, we demonstrate that the effect of abatacept is short-lived and that the inhibitory effects diminish markedly when treatment is ceased.
阿巴西普是一种共刺激阻滞剂,由与人IgG1的Fc区域相连的人CTLA-4细胞外部分组成,已被批准用于治疗类风湿性关节炎。通过损害T细胞上的CD28与抗原呈递细胞(APC)上的CD80/CD86之间的相互作用,其作用机制包括抑制滤泡辅助性T细胞(防止B细胞自身耐受性的破坏)、抑制细胞周期进程使T细胞处于一种被称为“诱导性幼稚”的状态以及减少树突状细胞的调节作用。然而,对于这些抑制作用可能持续多长时间了解较少,这对于患者的治疗应用来说是一个关键问题。在此,我们采用卵清蛋白诱导的迟发型超敏反应(DTH)小鼠模型,证明阿巴西普的作用是短暂的,并且当停止治疗时,抑制作用会显著减弱。