| First Author | del Rio ML | Year | 2005 |
| Journal | Eur J Immunol | Volume | 35 |
| Issue | 12 | Pages | 3545-60 |
| PubMed ID | 16285013 | Mgi Jnum | J:113923 |
| Mgi Id | MGI:3687870 | Doi | 10.1002/eji.200535232 |
| Citation | del Rio ML, et al. (2005) Antibody-mediated signaling through PD-1 costimulates T cells and enhances CD28-dependent proliferation. Eur J Immunol 35(12):3545-60 |
| abstractText | Programmed death-1 (PD-1, CD279) is a molecule expressed on activated T, B and myeloid cells. The role of the interaction of PD-1 ligands (PD-L1 and PD-L2) with PD-1 receptor and the type of signals (costimulatory or inhibitory) that are delivered is a subject of intense debate. Our study has characterized two monoclonal antibodies (mAb) against murine PD-1, termed clone 1H10 and clone 4F10, that recognized different epitopes from that of anti-PD-1, clone J43. We showed that neither of them inhibited anti-CD3-mediated proliferation, but 1H10 mAb induced direct T cell proliferation in the absence of any other stimulus. Moreover, PD-1 engagement with 1H10 mAb costimulated anti-CD3-mediated proliferation and enhanced anti-CD3/CD28 proliferation on both CD4+ and CD8+ T cells in the low range of anti-CD3 concentrations. Anti-PD-1-mediated proliferation induced with 1H10 mAb was also observed in vivo on CD4+ and CD8+ T cells, when CFSE-labeled splenocytes were adoptively transferred to irradiated syngeneic and allogeneic recipients. Overall, our data indicate that PD-1 might not only deliver negative signals to T cells upon interaction through one of its ligands, PD-L1 as reported, but also could costimulate T cells, suggesting a dual potential functional activity of the extracellular domains of this receptor. |
