PD-1 Protects against Inflammation and Myocyte Damage in T Cell-Mediated Myocarditis
- 15 May 2012
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 188 (10), 4876-4884
- https://doi.org/10.4049/jimmunol.1200389
Abstract
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.Keywords
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