| First Author | Zhao Y | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 6 | Pages | 1187-1203.e12 |
| PubMed ID | 37160118 | Mgi Jnum | J:337594 |
| Mgi Id | MGI:7491496 | Doi | 10.1016/j.immuni.2023.04.005 |
| Citation | Zhao Y, et al. (2023) cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8(+) T cell function and anti-tumor immunity. Immunity 56(6):1187-1203.e12 |
| abstractText | 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 (PKCtheta) 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. |
