Upon their activation, naïve CD8 T cells divide and differentiate into short-lived effector cells, relevant for exerting immune control, and long-lived memory cells, relevant for long-term immunity. The proportion of memory cells generated depends highly on the context of activation and whether the activated cell divides symmetrically or asymmetrically. However, how T cells control the extent of their asymmetry during their first division in response to contextual signals is not known. Using fluorescence loss in photo-bleaching (FLIP) experiments, we show that the metabolic and plasma membrane asymmetry of mitotic T cells depend on the regulated assembly of a lateral diffusion barrier in their endoplasmic reticulum (ER-) membrane. In asymmetrically dividing T cells, the degrees of asymmetry correlated tightly to barrier strength, whereas symmetrically dividing T cells did not establish such a barrier. Direct positive or negative interference with barrier assembly enhanced or abrogated metabolic and plasma membrane asymmetry, respectively, indicating that barrier strength is a direct and decisive determinant of mitotic asymmetry. Thus, together our data identify diffusion barrier-mediated compartmentalization as a mechanism for how asymmetric T cell regulate their long-term response as a function of the activatory context.

中文翻译：

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有丝分裂扩散屏障在调节活化 CD8 T 细胞不对称分裂中的作用

激活后，幼稚 CD8 T 细胞分裂并分化为与发挥免疫控制相关的短寿命效应细胞和与长期免疫相关的长寿命记忆细胞。产生的记忆细胞的比例在很大程度上取决于激活的背景以及激活的细胞是对称分裂还是不对称分裂。然而，T 细胞如何在响应上下文信号的第一次分裂期间控制其不对称程度尚不清楚。在光漂白 (FLIP) 实验中使用荧光损失，我们表明有丝分裂 T 细胞的代谢和质膜不对称性取决于其内质网 (ER-) 膜中横向扩散屏障的调节组装。在不对称分裂的 T 细胞中，不对称程度与屏障强度密切相关，而对称分裂的 T 细胞并没有建立这样的屏障。对屏障组装的直接正面或负面干扰分别增强或消除了代谢和质膜不对称性，表明屏障强度是有丝分裂不对称性的直接和决定性决定因素。因此，我们的数据一起将扩散屏障介导的区室化确定为不对称 T 细胞如何根据激活环境调节其长期反应的机制。