Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, USA.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
J Leukoc Biol. 2018 Nov;104(5):883-893. doi: 10.1002/JLB.2HI0617-229RRR. Epub 2018 Jul 31.
Inhibitory cell surface proteins on T cells are often dynamically regulated, which contributes to their physiologic function. PECAM-1 (CD31) is an inhibitory receptor that facilitates TGF-β-mediated suppression of T cell activity. It is well established in CD4 T cells that PECAM-1 is expressed in naïve recent thymic emigrants, but is down-regulated after acute T cell activation and absent from memory cells. The extent to which PECAM-1 expression is similarly regulated in CD8 T cells is much less well characterized. We evaluated T cells recovered from mice after infection with a model intracellular pathogen and determined that, in CD8 T cells, PECAM-1 expression was strongly down-regulated during acute infection but re-expressed to intermediate levels in memory cells. Down-regulation of PECAM-1 expression in CD8 T cells was transcriptionally regulated and affected by the strength and nature of TCR signaling. PECAM-1 was also detected on the surface of human activated/memory CD8 , but not CD4 T cells. These data demonstrate that PECAM-1 expression is dynamically regulated, albeit differently, in both CD4 and CD8 T cells. Furthermore, unlike memory CD4 T cells, memory CD8 T cells retain PECAM-1 expression and have the potential to be modulated by this inhibitory receptor.
T 细胞表面的抑制性蛋白通常是动态调节的,这有助于它们的生理功能。PECAM-1(CD31)是一种抑制性受体,它促进 TGF-β 介导的 T 细胞活性抑制。在 CD4 T 细胞中,PECAM-1 在幼稚的近期胸腺迁出细胞中表达,而在急性 T 细胞激活后下调,并且不存在于记忆细胞中,这一点已经得到充分证实。PECAM-1 在 CD8 T 细胞中的表达受到类似调节的程度则远不那么清楚。我们评估了感染模型细胞内病原体后的小鼠体内恢复的 T 细胞,结果表明,在 CD8 T 细胞中,PECAM-1 的表达在急性感染期间强烈下调,但在记忆细胞中重新表达到中等水平。CD8 T 细胞中 PECAM-1 表达的下调是转录调节的,并受 TCR 信号的强度和性质的影响。在人类激活/记忆 CD8 ,但不是 CD4 T 细胞的表面也检测到 PECAM-1。这些数据表明,PECAM-1 的表达在 CD4 和 CD8 T 细胞中都是动态调节的,尽管方式不同。此外,与记忆 CD4 T 细胞不同,记忆 CD8 T 细胞保留 PECAM-1 的表达,并有可能被这种抑制性受体调节。