Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, and Department of Periodontology, School of Stomatology, Capital Medical University, Beijing, China.
Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.
Arthritis Rheumatol. 2022 Oct;74(10):1699-1705. doi: 10.1002/art.42244. Epub 2022 Aug 31.
Sjögren's syndrome (SS) is a systemic autoimmune disease, and T cells play an important role in the initiation and perpetuation of the disease. In this study, we developed an immunotherapy for NOD/LtJ mice with SS-like symptoms by combining a transient depletion of CD4+ T cells with the administration of autoantigen-specific peptide Ro480.
NOD/LtJ mice were treated with single anti-CD4 monoclonal antibody (mAb) followed 2 days later by a series of 6 intraperitoneal injections of Ro480-494 every other day. Salivary flow rates were determined pre- and posttreatment once a week. Mice were euthanized 6 weeks after the initial anti-CD4 mAb treatment, salivary glands (SGs) were collected for analyses of histologic disease scores and inflammatory cell infiltration, polymerase chain reaction determination of genes was conducted, and flow cytometry analysis including major histocompatibility complex class II tetramer staining of immune cells was performed. In addition, adoptive transfer of Treg cells was administrated to investigate the function of the newly generating Treg cells in vivo.
The combination of anti-CD4 mAb with autoantigen-specific peptide Ro480 generated SSA/Ro antigen-specific Treg cells in vivo, which can suppress interferon-γ production of CD4+ T cells and inflammation infiltration in SGs and maintain the function of SGs.
Our findings provide a new approach to generating antigen-specific Treg cells in vivo for SS treatment, which may have implications for potential therapy for patients with SS.
干燥综合征（SS）是一种系统性自身免疫性疾病，T 细胞在疾病的起始和持续中起重要作用。在这项研究中，我们通过联合使用短暂耗尽 CD4+T 细胞和给予自身抗原特异性肽 Ro480-494，为具有 SS 样症状的 NOD/LtJ 小鼠开发了一种免疫疗法。
NOD/LtJ 小鼠用单克隆抗 CD4 抗体（mAb）治疗，2 天后每隔一天给予一系列 6 次 Ro480-494 腹腔内注射。在治疗前和每周一次的治疗后测定唾液流量率。在初始抗 CD4 mAb 治疗后 6 周，处死小鼠，收集唾液腺（SGs）进行组织学疾病评分和炎症细胞浸润分析，进行聚合酶链反应测定基因，并进行流式细胞术分析，包括免疫细胞主要组织相容性复合体 II 四聚体染色。此外，还进行了 Treg 细胞的过继转移，以研究体内新生成的 Treg 细胞的功能。
抗 CD4 mAb 与自身抗原特异性肽 Ro480 的联合使用在体内产生了 SSA/Ro 抗原特异性 Treg 细胞，可抑制 CD4+T 细胞的干扰素-γ产生和 SGs 中的炎症浸润，并维持 SGs 的功能。
我们的研究结果为 SS 治疗提供了一种在体内产生抗原特异性 Treg 细胞的新方法，这可能对 SS 患者的潜在治疗具有重要意义。
