PD-1-deficient mice developed enhanced T cell-mediated myocarditis with increased inflammation and myocardial damage compared with wild-type mice.
Does PD-1 deficiency exacerbate inflammation and myocyte damage in T cell-mediated myocarditis models?
The PD-1 pathway plays a critical role in limiting autoreactive T cell responses and protecting against inflammation and myocyte damage in the heart.
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.
Tarrio et al. (Tue,) conducted a other in T cell-mediated myocarditis. PD-1 deficiency vs. Wild-type was evaluated on Disease severity (inflammation and myocardial damage). PD-1-deficient mice developed enhanced T cell-mediated myocarditis with increased inflammation and myocardial damage compared with wild-type mice.