Objectives Successful early intervention in rheumatoid arthritis (RA) with the aim of resetting immunological tolerance requires a clearer understanding of how specificity, cellular kinetics and spatial behaviour shape the evolution of articular T cell responses. We aimed to define initial seeding of articular CD4+ T cell responses in early experimental arthritis, evaluating their dynamic behaviour and interactions with dendritic cells (DCs) in the inflamed articular environment. Methods Antigen-induced arthritis was used to model articular inflammation. Flow cytometry and PCR of T cell receptor (TCR) diversity genes allowed phenotypic analysis of infiltrating T cells. The dynamic interactions of T cells with joint residing DCs were visualised using intravital multiphoton microscopy. Results Initial recruitment of antigen-specific T cells into the joint was paralleled by accumulation of CD4+ T cells with diverse antigen-receptor expression and ability to produce tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) on mitogenic restimulation. A proportion of this infiltrate demonstrated slower motility speeds and engaged for longer periods with articular DCs in vivo. Abatacept treatment did not disrupt these interactions but did reduce T cell expression of inducible costimulatory (ICOS) molecule. We also demonstrated that non-specific CD4+ T cells could be recruited during these early articular events. Conclusions We demonstrate that CD4+ T cells engage with articular DCs supporting antigen specific T cell reactivation. This cellular dialogue can be targeted therapeutically to reduce local T cell activation.

中文翻译：

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可视化 CD4 T 细胞和 DCs 在炎症性关节炎演变中的相互作用

目标 以重新设置免疫耐受为目标的类风湿性关节炎 (RA) 早期成功干预需要更清楚地了解特异性、细胞动力学和空间行为如何影响关节 T 细胞反应的演变。我们旨在定义早期实验性关节炎中关节 CD4+ T 细胞反应的初始接种，评估它们在发炎的关节环境中的动态行为和与树突状细胞 (DC) 的相互作用。方法使用抗原诱导的关节炎来模拟关节炎症。T 细胞受体 (TCR) 多样性基因的流式细胞术和 PCR 允许对浸润性 T 细胞进行表型分析。使用活体多光子显微镜观察 T 细胞与关节驻留 DC 的动态相互作用。结果抗原特异性 T 细胞最初募集到关节中与 CD4+ T 细胞的积累平行，这些细胞具有不同的抗原受体表达和在有丝分裂再刺激时产生肿瘤坏死因子 α (TNFα) 和干扰素γ (IFNγ) 的能力。这种浸润的一部分表现出较慢的运动速度，并在体内与关节 DCs 接触的时间更长。阿巴西普治疗并未破坏这些相互作用，但确实降低了可诱导共刺激 (ICOS) 分子的 T 细胞表达。我们还证明在这些早期关节活动期间可以招募非特异性 CD4+ T 细胞。结论 我们证明 CD4+ T 细胞与支持抗原特异性 T 细胞再激活的关节 DC 结合。这种细胞对话可以在治疗上靶向以减少局部 T 细胞活化。