T cell co-stimulation is important for the maintenance of immunologic tolerance. Co-inhibitory receptors including programmed cell death-1 (PD-1) confer peripheral tolerance to prevent autoimmunity. SAP (SH2D1A) is an adaptor molecule that is important in T cell signaling and has been shown to interact with signaling lymphocytic activation molecule (SLAM) family receptors also in the context of self-tolerance. We recently reported that SAP interferes with PD-1 function. In the current study, we investigated the levels of SAP and PD-1 in patients with rheumatoid arthritis (RA) to further understand what role they play in disease activity. We observed increased SAP levels in lymphocytes of RA patients and found that PD-1 levels correlated positively with RA disease activity. Additionally, we found that SAP interacts with CD28 to inhibit T cell signaling in vitro. This work demonstrates a putative molecular mechanism for SAP mediated PD-1 inhibition.

T 细胞共刺激对于维持免疫耐受很重要。包括程序性细胞死亡-1 (PD-1) 在内的共抑制受体赋予外周耐受性以防止自身免疫。SAP (SH2D1A) 是一种衔接分子，在 T 细胞信号传导中很重要，并且已显示在自我耐受的情况下也与信号传导淋巴细胞激活分子 (SLAM) 家族受体相互作用。我们最近报道了 SAP 会干扰 PD-1 功能。在目前的研究中，我们调查了类风湿关节炎 (RA) 患者的 SAP 和 PD-1 水平，以进一步了解它们在疾病活动中的作用。我们观察到 RA 患者淋巴细胞中 SAP 水平升高，发现 PD-1 水平与 RA 疾病活动呈正相关。此外，我们发现 SAP 与 CD28 相互作用以在体外抑制 T 细胞信号传导。这项工作证明了 SAP 介导的 PD-1 抑制的推定分子机制。