低剂量IL-2治疗自身免疫病中调节性T细胞应答异质性的研究进展
Research Progress on Heterogeneity of Regulatory T Cell Responses to Low-Dose IL-2 Therapy in Autoimmune Diseases
DOI: 10.12677/acm.2025.15123587, PDF,    科研立项经费支持
作者: 胡泽澎：绍兴文理学院医学院，浙江 绍兴；绍兴市人民医院暨绍兴文理学院附属第一医院风湿免疫科，浙江 绍兴；王 鑫*：绍兴市人民医院暨绍兴文理学院附属第一医院风湿免疫科，浙江 绍兴
关键词: 低剂量IL-2；调节性T细胞；自身免疫病；治疗异质性；Low-Dose IL-2； Regulatory T Cells； Autoimmune Diseases； Therapeutic Heterogeneity
摘要: 白介素-2 (IL-2)是一种多效性细胞因子，在免疫系统中扮演着双重角色。一方面，它是效应T细胞(Teff)和自然杀伤(NK)细胞活化与扩增的关键因子；另一方面，它也是维持调节性T细胞(Treg)存活、功能和稳定的核心信号。基于Treg细胞表面高亲和力IL-2受体(CD25)的表达，低剂量IL-2 (ld-IL-2)能够选择性激活和扩增Treg，从而恢复免疫耐受，这为治疗自身免疫病提供了极具吸引力的新策略。在1型糖尿病、系统性红斑狼疮、类风湿关节炎等多种自身免疫病的临床试验中，ld-IL-2治疗已显示出良好的安全性和初步疗效。然而，临床观察发现，不同个体、不同病种甚至同一病种的不同患者对ld-IL-2的治疗反应存在显著异质性，表现为Treg扩增程度、功能状态及临床结局的差异。本综述系统梳理了ld-IL-2治疗的机制基础，重点探讨了Treg应答异质性的临床表现、潜在机制(包括疾病内在因素、个体免疫状态、药物动力学/药效学、肠道微生物等)，并展望了通过生物标志物指导的个体化治疗、新型IL-2变体以及联合治疗等策略来克服异质性、优化治疗效果的未来前景。
Abstract: Interleukin-2 (IL-2) is a pleiotropic cytokine with a dual role in the immune system. On one hand, it is a key factor for the activation and expansion of effector T cells (Teff) and natural killer (NK) cells; on the other hand, it is a core signal for the survival, function, and stability of regulatory T cells (Treg). Based on the high-affinity IL-2 receptor (CD25) expression on Tregs, low-dose IL-2 (ld-IL-2) can selectively activate and expand Tregs, thereby restoring immune tolerance, which presents an attractive new strategy for treating autoimmune diseases. Clinical trials of ld-IL-2 in various autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis, have demonstrated good safety and preliminary efficacy. However, clinical observations have revealed significant heterogeneity in the treatment response to ld-IL-2 among different individuals, different diseases, and even different patients with the same disease, manifesting as differences in the degree of Treg expansion, functional status, and clinical outcomes. This review systematically outlines the mechanistic basis of ld-IL-2 therapy, focusing on the clinical manifestations and potential mechanisms underlying the heterogeneity of Treg responses (including disease-intrinsic factors, individual immune status, pharmacokinetics/pharmacodynamics, gut microbiota, etc.). It also explores future directions for overcoming this heterogeneity and optimizing therapeutic efficacy, such as biomarker-guided personalized therapy, novel IL-2 variants, and combination therapies.
文章引用：胡泽澎, 王鑫. 低剂量IL-2治疗自身免疫病中调节性T细胞应答异质性的研究进展[J]. 临床医学进展, 2025, 15(12): 1730-1738. https://doi.org/10.12677/acm.2025.15123587

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