在共刺激阻塞下,口服抗原暴露会诱导Treg细胞建立免疫耐受性
Masaya Arai1, Ryoji Kawakami1,2, Yamami Nakamura1
1Department of Experimental Immunology, Immunology Frontier Research Center, The University of Osaka, Osaka, Japan.
The Journal of experimental medicine
|October 21, 2025
概括
口服抗原养会产生调节性T (Treg) 细胞,但在原始宿主中很难诱导耐受性. 使用CTLA4-Ig阻断CD28共刺激促进稳定的CD101+Treg细胞生成以获得全身口服耐受性.
科学领域:
- 免疫学 免疫学 免疫学
- T细胞生物学T细胞生物学
- 口服耐受性诱导口服耐受性诱导
背景情况:
- 对抗原特异性口服耐受性对于预防免疫反应至关重要.
- 诱导口服耐受性在已经对抗原进行了初始化的个体中具有挑战性.
研究的目的:
- 通过口服抗原养来研究产生稳定调节性T (Treg) 细胞的方法.
- 建立全身抗原特异性口服耐受性,即使在抗原敏感的宿主中.
主要方法:
- 将含有抗原的食给小鼠,以诱导外围衍生Treg (pTreg) 细胞.
- 分析Treg特征基因 (例如Foxp3) 中的表观基因组变化.
- 在体外和体内产生CD101+ Treg细胞,通过阻断Treg诱导过程中CD28的辅助刺激.
主要成果:
- 口服抗原养产生了具有稳定的抑制功能和组织适应性质的pTreg细胞.
- 停止抗原养减少了pTreg细胞,阻碍了耐受性.
- 阻止CD28信号传递 (使用CTLA4-Ig) 促进了抗原特异性T细胞分化为CD101+ pTreg细胞,促进了敏感小鼠的口服耐受性.
结论:
- 连续的口服抗原暴露与CD28阻断相结合,有效产生功能稳定的CD101+ pTreg细胞.
- 这种方法建立了全身抗原特异性耐受性,即使在抗原过敏宿主中也是如此.
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