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癌症抵抗性裸鼠中T细胞的进化

Tzuhua D Lin¹, Nimrod D Rubinstein², Nicole L Fong¹

¹Calico Life Sciences LLC, South San Francisco, California, CA, USA.

Nature communications

|April 11, 2024

概括

裸鼠拥有独特的免疫系统,有大量循环的马-三角形T细胞 (γδT细胞) 和其他T细胞的有限多样性,这可能解释了它们的抗癌性和寿命.

科学领域:

免疫学免疫学免疫学
进化生物学进化生物学
进行比较基因组学.

背景情况:

裸鼠 (NMRs) 具有显著的寿命和抗癌能力.
他们的免疫系统,特别是T细胞和自然杀手 (NK) 细胞,被认为是这些独特的表型的基础.
众所周知,NMR缺乏NK细胞,但它们的T细胞子集仍未得到充分研究.

研究的目的:

为了研究裸露的鼠中的T细胞子集.
了解与长寿和抗癌能力相关的NMR免疫系统的进化适应.
描述NMRT细胞的功能,多样性和胸膜发育.

主要方法:

单细胞转录组学用于分析循环的免疫细胞.
单细胞T细胞受体测序以评估T细胞克隆类型多样性.
用小鼠模型对NMR胸腺大小和卷积进行比较分析.

主要成果:

核磁共振具有大量的马-三角形T细胞 (γδT细胞) 的循环群体,与老鼠和人类不同,这些细胞主要存在于外围组织中.
在NMR中,细胞毒性γδT细胞的一个子集显示出一种主要的克隆型.
传统的CD8αβT细胞在NMR中显示出有限的克隆类型多样性.
核磁共振胸腺较小于小鼠,但遵循类似的发育轨迹.

结论:

核磁共振免疫系统已经适应了,可能是由于细胞内病原体的选择性压力放松.
细胞毒性 γδT 细胞的突出性可能有助于NMRs的异常抗癌性和寿命.
这些发现突显了NMR免疫系统中独特的进化策略.

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