@article {542426,
	title = {Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart.},
	journal = {Circulation},
	volume = {116},
	number = {18},
	year = {2007},
	month = {2007 Oct 30},
	pages = {2062-71},
	abstract = {BACKGROUND: PD-L1 and PD-L2 are ligands for the inhibitory receptor programmed death-1 (PD-1), which is an important regulator of immune responses. PD-L1 is induced on cardiac endothelial cells under inflammatory conditions, but little is known about its role in regulating immune injury in the heart.

METHODS AND RESULTS: Cytotoxic T-lymphocyte-mediated myocarditis was induced in mice, and the influence of PD-L1 signaling was studied with PD-L1/L2-deficient mice and blocking antibodies. During cytotoxic T-lymphocyte-induced myocarditis, the upregulation of PD-L1 on cardiac endothelia was dependent on T-cell-derived interferon-gamma, and blocking of interferon-gamma signaling worsened disease. Genetic deletion of both PD-1 ligands [PD-L1/2(-/-)], as well as treatment with PD-L1 blocking antibody, transformed transient myocarditis to lethal disease, in association with widespread polymorphonuclear leukocyte-rich microabscesses but without change in cytotoxic T-lymphocyte recruitment. PD-L1/2(-/-) mice reconstituted with bone marrow from wild-type mice remained susceptible to severe disease, which demonstrates that PD-L1 on non-bone marrow-derived cells confers the protective effect. Finally, depletion of polymorphonuclear leukocytes reversed the enhanced susceptibility to lethal myocarditis attributable to PD-L1 deficiency.

CONCLUSIONS: Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune-mediated cardiac injury and polymorphonuclear leukocyte inflammation.},
	keywords = {Animals, Antigens, CD274, Antigens, CD80, CD8-Positive T-Lymphocytes, Endothelial Cells, Inflammation, Inflammation Mediators, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myocarditis, Neutrophils, Peptides, Signal Transduction},
	issn = {1524-4539},
	doi = {10.1161/CIRCULATIONAHA.107.709360},
	author = {Grabie, Nir and Gotsman, Israel and DaCosta, Rosa and Pang, Hong and Stavrakis, George and Butte, Manish J and Keir, Mary E and Freeman, Gordon J and Sharpe, Arlene H and Lichtman, Andrew H}
}
