Chen Guangjie, Li Ningli, Zang Ying C Q, Zhang Dongqing, He Dongyi, Feng Guozhang, Ni Liqing, Xu Rong, Wang Li, Shen Baihua, Zhang Jingwu Z
Shanghai Institute of Immunology, JiaoTong University School of Medicine, Shanghai, China.
Arthritis Rheum. 2007 Feb;56(2):453-63. doi: 10.1002/art.22316.
This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA).
Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months.
T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,V(beta)2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10-secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor alpha-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters.
These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients.
开展这项初步临床研究以调查T细胞疫苗接种在类风湿关节炎（RA）患者中诱导调节性免疫反应的作用。
选择具有病理相关性的自体滑膜T细胞，经照射使其失活，然后用于疫苗接种。15名患者在12个月内通过6次皮下接种接受T细胞疫苗接种。
T细胞疫苗接种导致诱导出针对T细胞疫苗的CD4+调节性T细胞（Tregs）和CD8+细胞毒性T细胞。产生白细胞介素-10（IL-10）并高表达转录因子Foxp3的CD4+、Vβ2+ Tregs出现选择性扩增，这与治疗患者中过表达的BV14+ T细胞耗竭相一致。发现T细胞疫苗接种诱导的分泌IL-10的CD4+ Tregs与源自IL-2受体α链的肽特异性反应。T细胞疫苗接种后，CD4+ T细胞中Foxp3的表达水平以及CD4+、CD25+ Tregs的抑制活性显著升高。观察到的调节性免疫反应总体上与治疗患者的临床改善相关。在一项意向性分析中，15名患者中有10名（66.7%）显示出显著反应，定义为符合美国风湿病学会50%改善标准，同时RA相关实验室参数也有明显改善。
这些发现表明，T细胞疫苗接种可诱导调节性免疫反应，这与RA患者临床和实验室指标的改善相关。
