Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2021 Feb 24;12:630204. doi: 10.3389/fimmu.2021.630204. eCollection 2021.
Regulatory T (T) cells are essential to maintain immune homeostasis in the intestine and T cell dysfunction is associated with several inflammatory and autoimmune disorders including inflammatory bowel disease (IBD). Efforts using low-dose (LD) interleukin-2 (IL-2) to expand autologous T cells show therapeutic efficacy for several inflammatory conditions. Whether LD IL-2 is an effective strategy for treating patients with IBD is unknown. Recently, we demonstrated that LD IL-2 was protective against experimental colitis in immune humanized mice in which human CD4 T cells were restricted to human leukocyte antigen (HLA). Whether HLA restriction is required for human T cells to ameliorate colitis following LD IL-2 therapy has not been demonstrated. Here, we show that treatment with LD IL-2 reduced 2,4,6-trinitrobenzensulfonic acid (TNBS) colitis severity in NOD. (NSG) mice reconstituted with human CD34 hematopoietic stem cells. These data demonstrate the utility of standard immune humanized NSG mice as a pre-clinical model system to evaluate therapeutics targeting human T cells to treat IBD.
调节性 T（T）细胞对于维持肠道免疫稳态至关重要，T 细胞功能障碍与几种炎症和自身免疫性疾病有关，包括炎症性肠病（IBD）。使用低剂量（LD）白细胞介素 2（IL-2）来扩增自体 T 细胞的努力显示出对几种炎症情况的治疗效果。低剂量 IL-2 是否是治疗 IBD 患者的有效策略尚不清楚。最近，我们证明 LD IL-2 可预防免疫人源化小鼠中的实验性结肠炎，其中人类 CD4 T 细胞受到人类白细胞抗原（HLA）的限制。在 LD IL-2 治疗后，HLA 限制是否是人类 T 细胞缓解结肠炎所必需的尚未得到证明。在这里，我们显示用 LD IL-2 治疗可降低用人类 CD34 造血干细胞重建的 NOD.（NSG）小鼠的 2,4,6-三硝基苯磺酸（TNBS）结肠炎严重程度。这些数据证明了标准免疫人源化 NSG 小鼠作为临床前模型系统的实用性，可用于评估针对人类 T 细胞治疗 IBD 的治疗方法。
