| First Author | Tarrio ML | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 10 | Pages | 4876-84 |
| PubMed ID | 22491251 | Mgi Jnum | J:188681 |
| Mgi Id | MGI:5441426 | Doi | 10.4049/jimmunol.1200389 |
| Citation | Tarrio ML, et al. (2012) PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J Immunol 188(10):4876-84 |
| abstractText | PD-1, a member of the CD28 family of immune regulatory molecules, is expressed on activated T cells, interacts with its ligands, PD-L1/B7-H1 and PD-L2/B7-DC, on other cells, and delivers inhibitory signals to the T cell. We studied the role of this pathway in modulating autoreactive T cell responses in two models of myocarditis. In a CD8(+) T cell-mediated adoptive transfer model, we found that compared with Pd1(+/+) CD8(+) T cells, Pd1(-/-) CD8(+) T cells cause enhanced disease, with increased inflammatory infiltrate, particularly rich in neutrophils. Additionally, we show enhanced proliferation in vivo and enhanced cytotoxic activity of PD-1-deficient T lymphocytes against myocardial endothelial cells in vitro. In experimental autoimmune myocarditis, a disease model dependent on CD4(+) T cells, we show that mice lacking PD-1 develop enhanced disease compared with wild-type mice. PD-1-deficient mice displayed increased inflammation, enhanced serum markers of myocardial damage, and an increased infiltration of inflammatory cells, including CD8(+) T cells. Together, these studies show that PD-1 plays an important role in limiting T cell responses in the heart. |
