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具有MHCII类特异性化学抗原受体的Tregs可以预防小鼠自身免疫糖尿病

Justin A Spanier^1,2,3, Vivian Fung^4,5, Christine M Wardell^4,5

¹Center for Immunology.

The Journal of clinical investigation

|August 10, 2023

概括

工程调节性T细胞 (Tregs) 具有针对小岛抗原的仿真抗原受体 (CAR),有望预防1型糖尿病. 这种方法增强了Treg功能,并在临床前模型中预防了自身免疫糖尿病.

科学领域:

免疫学免疫学免疫学
内分泌学在内分泌学.
细胞疗法细胞疗法

背景情况:

使用调节性T细胞 (Tregs) 的采用免疫疗法是1型糖尿病的潜在治疗方法.
与多克隆Tregs相比,小岛抗原特异性Tregs提供了更好的治疗效果,但它们在自然界的有限存在阻碍了临床使用.

研究的目的:

使用仿真抗原受体 (CAR) 设计具有对岛屿抗原特异性的调节性T细胞 (Tregs).
评估这些工程Tregs在预防NOD小鼠自身免疫糖尿病中的治疗潜力.

主要方法:

一种仿制抗原受体 (CAR),InsB-g7,被设计为向由IAg7 MHCII类等位基呈现的胰岛素B链10-23.
通过四聚体染色和T细胞增殖试验证实了InsB-g7 CAR的特异性.
通过测量它们对T细胞增殖,IL-2产生和树突细胞成熟的影响,评估了InsB-g7CARTregs的抑制功能.

主要成果:

胰岛素B 10-23刺激增强了InsB-g7 CAR Tregs的抑制功能.
工程Tregs降低了T细胞的增殖和IL-2的产生,并降低了树突细胞上的共刺激分子表达.
InsB-g7 CAR Tregs的共转移在免疫缺陷NOD小鼠中预防了通过采用T细胞转移诱导的糖尿病,并在WT NOD小鼠中阻止了自发糖尿病.

结论:

通过类似T细胞受体的CAR来对岛屿抗原进行工程Treg特异性是一种可行的策略.
这种方法有望预防自身免疫性糖尿病,为1型糖尿病提供潜在的治疗途径.

关键词:

这是一种自身免疫力.糖尿病糖尿病糖尿病免疫学免疫学免疫学免疫治疗是一种免疫疗法.宽容是一种宽容.

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