瑞士苏黎世大学Onur Boyman研究团队发现，白介素-2免疫疗法揭示具有不同功能和组织归巢特征的人类调节性T细胞亚群。这一研究成果于2024年8月12日在线发表在国际学术期刊《免疫》上。

研究人员表示，由于其对免疫调节性CD4⁺调节性T（Treg）细胞的刺激潜力，低剂量白介素-2（IL-2）免疫疗法在自身免疫疾病的治疗中引起了相当大的关注。

在一项针对系统性红斑狼疮（SLE）患者的研究者发起的单臂非安慰剂对照II期临床试验中，研究人员生成了低剂量IL-2在体内对人类免疫反应的综合图谱。研究人员通过成像质谱流式细胞术、高参数流式细胞术、转录组学和靶向血清蛋白组学对循环和皮肤免疫细胞进行了深入研究。

低剂量IL-2刺激了多种循环免疫细胞，包括在SLE患者皮肤中出现的具有皮肤归巢表型的Treg细胞，这些细胞与内皮细胞紧密相互作用。

表面蛋白和转录组分析揭示了不同的IL-2驱动的Treg细胞激活程序，包括肠道归巢CD38⁺、皮肤归巢HLA-DR⁺和高度增殖的炎症归巢CD38⁺ HLA-DR⁺ Treg细胞。总体而言，这些数据定义了对IL-2免疫疗法有反应的人类Treg细胞亚群。

附：英文原文

Title: Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics

Author: Miro E. Raeber, Dominic P. Caspar, Yves Zurbuchen, Nannan Guo, Jonas Schmid, Jan Michler, Alina C. Martin, Urs C. Steiner, Andreas E. Moor, Frits Koning, Onur Boyman

Issue&Volume: 2024-08-12

Abstract: Due to its stimulatory potential for immunomodulatory CD4+ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38+, skin-homing HLA-DR+, and highly proliferative inflammation-homing CD38+ HLA-DR+ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.

DOI: 10.1016/j.immuni.2024.07.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00365-0