| First Author | Sugiura D | Year | 2019 |
| Journal | Science | Volume | 364 |
| Issue | 6440 | Pages | 558-566 |
| PubMed ID | 31000591 | Mgi Jnum | J:277405 |
| Mgi Id | MGI:6315984 | Doi | 10.1126/science.aav7062 |
| Citation | Sugiura D, et al. (2019) Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses. Science 364(6440):558-566 |
| abstractText | Targeted blockade of PD-1 with immune checkpoint inhibitors can activate T cells to destroy tumors. PD-1 is believed to function mainly at the effector, but not in the activation, phase of T cell responses, yet how PD-1 function is restricted at the activation stage is currently unknown. Here we demonstrate that CD80 interacts with PD-L1 in cis on antigen-presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 cannot engage PD-1 to inhibit T cell activation when APCs express substantial amounts of CD80. In knock-in mice in which cis-PD-L1/CD80 interactions do not occur, tumor immunity and autoimmune responses were greatly attenuated by PD-1. These findings indicate that CD80 on APCs limits the PD-1 coinhibitory signal, while promoting CD28-mediated costimulation, and highlight critical components for induction of optimal immune responses. |
