CD8αα+ T cells show amoeboid shape and frequent morphological change in?vitro, and localize to small intestinal intraepithelial region in?vivo
CD8αα+ T cells show amoeboid shape and frequent morphological change in?vitro, and localize to small intestinal intraepithelial region in?vivo
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CD8αα+ T细胞在体外表现出变形虫形状和频繁的形态变化，在体内定位于小肠上皮内区域
DOI：
10.1016/j.bbrc.2019.12.021
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发表时间：
2020
影响因子：
3.1
通讯作者：
Watanabe Mamoru
中科院分区：
文献类型：
--
作者：
Takei Yuria;Nemoto Yasuhiro;Morikawa Ryo;Tanaka Shohei;Oshima Shigeru;Nagaishi Takashi;Okamoto Ryuichi;Tsuchiya Kiichiro;Nakamura Tetsuya;Watanabe Mamoru
上皮内淋巴细胞（IEL）在肠道免疫系统中非常独特。它们包括γδT细胞和CD 4-CD 8-TCRαβ+T细胞（双阴性：DNT），除了CD 4+和CD 8 +T细胞外，这两种细胞都对肠道具有特异性。IEL存在于肠上皮细胞的单层内，并在固有层（LP）和上皮内（IE）区域之间动态移动。IEL亚群的定位和运动模式以及调节因素尚不清楚。在这里，我们开发了一种新的体外活体成像系统，并量化了IEL子集之间的运动性和形态学变化。我们确定了CD 8 αα为关键调节因子。IEL，尤其是γδ和DNT细胞，在体外表现为变形虫状，形态变化频繁，而MLN和SP中的T细胞多为圆形。TCR信号、IL-15、肠道微生物、CCL 25和整合素αEβ7的表达对IEL的体外运动不是必需的。CD 8 αα+细胞比CD 8 αα-细胞具有更高的运动性和更大的形态学变化。连续转移的CD 8 αα+ CD 4-IEL定位于受体NSG小鼠的IE区，而CD 8 αα-CD 4-IEL定位于LP区。结果表明，CD 8 αα/TL信号是IELs在体内定位于IE区的必要信号。CD 8 αα/TL可能是增加IEL数量的有效靶点，从而保护肠道免受感染、过敏、肿瘤发生或炎症。
Intraepithelial lymphocytes (IELs) are very unique in the intestinal immune system. They include γδT cells and CD4–CD8–TCRαβ+T cells (double negative: DNT), both of which are specific for the intestine, in addition to CD4+and CD8+T cells. IELs exist within the monolayer of the intestinal epithelial cells and dynamically move between lamina propria (LP) and intraepithelial (IE) region. The localization and movement patterns of IEL subsets and the regulatory factors have been unknown. Here, we developed a novel in vitro live imaging system and quantified the motility and morphological changes among subsets of IELs. We identified CD8αα as the key regulatory factor. IELs, especially γδ and DNT cells, showed amoeboid shape and frequent morphological change, while most T cells in MLN or SP showed round shape in vitro. TCR signal, IL-15, gut microbes, CCL25, and integrin αEβ7 expression were non-essential for IEL movement in vitro. CD8αα+cells showed higher motility and larger morphological changes than CD8αα–cells. Adoptive transferred CD8αα+CD4-IELs localized to IE region of recipient NSG mice, while CD8αα–CD4-IELs localized to the LP. Our results showed that the CD8αα/TL signal is essential for the localization of IELs to IE region in vivo. CD8αα/TL may be an effective target to increase the number of IELs, which protects against intestinal infection, allergy, tumorigenesis or inflammation.