| RRC ID |
69680
|
| 著者 |
Sugiura D, Okazaki IM, Maeda TK, Maruhashi T, Shimizu K, Arakaki R, Takemoto T, Ishimaru N, Okazaki T.
|
| タイトル |
PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity.
|
| ジャーナル |
Nat Immunol
|
| Abstract |
Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules.
|
| 巻・号 |
23(3)
|
| ページ |
399-410
|
| 公開日 |
2022-3-1
|
| DOI |
10.1038/s41590-021-01125-7
|
| PII |
10.1038/s41590-021-01125-7
|
| PMID |
35145298
|
| MeSH |
Animals
Autoimmune Diseases*
Autoimmunity
B7-1 Antigen
B7-H1 Antigen / metabolism
Mice
Neoplasms*
Programmed Cell Death 1 Receptor / metabolism
T-Lymphocytes
|
| IF |
20.479
|
| リソース情報 |
| ヒト・動物細胞 |
RAJI(RCB1647) |
