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 peripheral tissues. 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 remodeling driven 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, loss of 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.

B7 配体（CD80 和 CD86）由专业抗原呈递细胞 (APC) 表达，反式激活 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。这就提出了 CD28 共刺激是否以及如何在外周组织中发生的问题。在此，我们报道，由于磷酸肌醇 3 激酶 (PI3K) 和 sorting-nexin-9 (SNX9) 驱动的膜重塑， CD8 ⁺ T 细胞在免疫突触的膜内陷处展示出与 CD28 顺式相互作用的 B7 配体。 cis- B7:CD28 相互作用通过蛋白激酶 C theta (PKCθ) 触发 CD28 信号传导，并促进 CD8 ⁺ T 细胞存活、迁移和细胞因子产生。在小鼠肿瘤模型中，T细胞固有的顺式-B7:CD28相互作用的丧失减少了肿瘤内T细胞并加速了肿瘤生长。因此，CD8 ⁺ T 细胞上的 B7 配体可以在外周组织中引起顺式细胞自主 CD28 共刺激，表明顺式信号传导是增强 T 细胞功能的一般机制。