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调控性CD4⁺ T细胞识别主要基因相容性复杂的II类分子受限的阿波利波蛋白B的片

Takayuki Kimura¹, Kouji Kobiyama¹, Holger Winkels¹

¹Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, CA (T.K., K.K., H.W., K.T., J.M., M.V., D.W., C.R., M.O., K.L.).

|March 29, 2018

概括

在健康个体中,Apolipoprotein B (ApoB) 18特异性CD4+T细胞主要是调节性T细胞 (Tregs). 在患有亚临床心血管疾病的患者中,这些Tregs表达额外的转录因子,突出显示ApoB p18是动脉样硬化的关键Treg表位.

科学领域:

免疫学
心血管疾病研究
T细胞生物学

背景情况:

CD4+ T细胞在动脉样硬化中至关重要,但它们的特定抗原尚不清楚.
在动物模型中,Apolipoprotein B (ApoB) 免疫表现出甲状腺保护作用.
一种保存的人类和小鼠ApoB,p18,与MHCII类分子结合.

研究的目的:

研究ApoB特异性CD4+T细胞在动脉样硬化中的作用.
在 ApoB 中识别特定的 T 细胞表位.
描述响应ApoB p18的T细胞的表型和功能.

主要方法:

开发用于检测人类和小鼠APOB特异性T细胞的p18四聚体.
包括转录因子和细胞因子在内的T细胞表型的流细胞测量分析.
在p18疫苗接种后对Apoe-/小鼠进行动脉硬性负担评估.

主要成果:

在健康人群中,p18特异性的CD4+T细胞主要是Foxp3+调节性T细胞 (Tregs).
患有亚临床心血管疾病的捐赠者显示Tregs共表达T-bet或RORγt.
在Apoe-/小鼠中,p18免疫诱导了Tregs和降低了动脉样硬化,扩大了IL-10产生Tregs.

结论:

在亚临床心血管疾病中,APOB p18特定的CD4+T细胞从Treg转移到表达其他转录因子.
ApoB被确定为第一个涉及人类和小鼠动脉样硬化的Treg表位.
这一发现为动脉样硬化提供了潜在的治疗点.

关键词:

抗原特异性 apoB-100的使用情况动脉样硬化监管T细胞接种疫苗

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