小柯机器人

美国加州大学圣地亚哥分校Enfu Hui、Jack D. Bui、Yunlong Zhao小组的最新研究发现，cis-B7:CD28在内陷突触膜上的相互作用提供了CD28共刺激，并促进CD8⁺ T细胞功能和抗肿瘤免疫。相关论文于2023年5月8日发表在《免疫》杂志上。

研究人员发现CD8⁺ T细胞在免疫突触膜内陷处发生B7配体与CD28相互作用，这是由磷酸肌醇-3-激酶（PI3K）和分选-连接蛋白-9（SNX9）诱导的膜重塑产生。顺式-B7:CD28相互作用通过蛋白激酶C θ（PKCθ）诱导CD28信号传导，促进CD8⁺ T细胞的存活、迁移和细胞因子产生。

在小鼠肿瘤模型中T细胞的顺式-B7：CD28相互作用丧失导致肿瘤内T细胞减少并加速肿瘤生长。因此，CD8⁺ T细胞上的B7配体可以诱导外周组织细胞自主产生顺式CD28共刺激，这表明顺式信号传导是增强T细胞功能的一种机制。

据悉，由特异抗原呈递细胞（APC）表达的B7配体（CD80和CD86）激活反式T细胞上的主要共刺激受体CD28。然而在外周组织中，表达B7配体的APC相对稀少。这就引申出CD28共刺激是否以及如何在外周组织中出现。

附：英文原文

Title: cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8+ T cell function and anti-tumor immunity

Author: Yunlong Zhao, Christine Caron, Ya-Yuan Chan, Calvin K. Lee, Xiaozheng Xu, Jibin Zhang, Takeya Masubuchi, Chuan Wu, Jack D. Bui, Enfu Hui

Issue&Volume: 2023-05-08

Abstract: B7 ligands (CD80 and CD86), expressed by professional antigen-presenting cells (APCs),activate the main co-stimulatory receptor CD28 on T cells in trans. However, in peripheral tissues, APCs expressing B7 ligands are relatively scarce.This raises the questions of whether and how CD28 co-stimulation occurs in peripheraltissues. Here, we report that CD8+ T cells displayed B7 ligands that interacted with CD28 in cis at membrane invaginations of the immunological synapse as a result of membrane remodelingdriven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9). cis-B7:CD28 interactions triggered CD28 signaling through protein kinase C theta (PKCθ)and promoted CD8+ T cell survival, migration, and cytokine production. In mouse tumor models, lossof T cell-intrinsic cis-B7:CD28 interactions decreased intratumoral T cells and accelerated tumor growth.Thus, B7 ligands on CD8+ T cells can evoke cell-autonomous CD28 co-stimulation in cis in peripheral tissues, suggesting cis-signaling as a general mechanism for boosting T cell functionality.

DOI: 10.1016/j.immuni.2023.04.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00173-5

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