| First Author | Bu DX | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 5 | Pages | 1100-7 |
| PubMed ID | 21393583 | Mgi Jnum | J:191478 |
| Mgi Id | MGI:5461802 | Doi | 10.1161/ATVBAHA.111.224709 |
| Citation | Bu DX, et al. (2011) Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol 31(5):1100-7 |
| abstractText | OBJECTIVE: Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We studied the contribution of the PD-1 pathway to regulation of T cells that promote atherosclerotic lesion formation and inflammation. METHODS AND RESULTS: We show that compared with Ldlr-/- control mice, Pd1-/-Ldlr-/- mice developed larger lesions with more abundant CD4+ and CD8+ T cells and macrophages, accompanied by higher levels of serum tumor necrosis factor-alpha. Iliac lymph node T cells from Pd1-/-Ldlr-/- mice proliferated more to alphaCD3 or oxidized low-density lipoprotein stimulation compared with controls. CD8+ T cells from Pd1-/-Ldlr-/- mice displayed more cytotoxic activity compared with controls in vivo and in vitro. Administration of a blocking anti-PD-1 antibody increased lesional inflammation in hypercholesterolemic Ldlr-/- mice with more lesional T cells and more activated T cells in paraaortic lymph nodes. The changes in lesional T-cell content when PD-1 was absent or blocked were also observed in bone marrow chimeric Ldlr-/- mice lacking PD-L1 and PD-L2 on hematopoietic cells. CONCLUSIONS: PD-1 has an important role in downregulating proatherogenic T-cell responses, and blockade of this molecule for treatment of viral infections or cancer may increase risk of cardiovascular complications. |
