Blockade of the Interaction Between PD-1 and PD-L1 Accelerates Graft Arterial Disease in Cardiac Allografts

BACKGROUND—Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS...

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Veröffentlicht in:	Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2004-11, Vol.24 (11), p.2057-2062
Hauptverfasser:	Koga, Noritaka, Suzuki, Jun-ichi, Kosuge, Hisanori, Haraguchi, Go, Onai, Yasuyuki, Futamatsu, Hideki, Maejima, Yasuhiro, Gotoh, Ryo, Saiki, Hitoshi, Tsushima, Fumihiko, Azuma, Miyuki, Isobe, Mitsuaki
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antibodies, Blocking - adverse effects Antibodies, Monoclonal - adverse effects Antigens, Surface - biosynthesis Antigens, Surface - immunology Antigens, Surface - metabolism Aorta - chemistry Aorta - cytology Aorta - metabolism Apoptosis Regulatory Proteins Atherosclerosis (general aspects, experimental research) B7-1 Antigen - biosynthesis B7-1 Antigen - immunology B7-1 Antigen - metabolism B7-H1 Antigen Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Proliferation Cells, Cultured Coronary Disease - immunology Coronary Disease - metabolism Cytokines - biosynthesis Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Graft Rejection - immunology Graft Rejection - metabolism Heart Transplantation Interferon-gamma - immunology Lymphocyte Activation - immunology Male Medical sciences Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - immunology Membrane Glycoproteins - metabolism Mice Mice, Inbred C57BL Muscle, Smooth, Vascular - chemistry Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - chemistry Myocytes, Smooth Muscle - metabolism Peptides - immunology Peptides - metabolism Programmed Cell Death 1 Receptor Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart T-Lymphocytes - metabolism T-Lymphocytes - physiology Transplantation, Homologous
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Zusammenfassung:	BACKGROUND—Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS AND RESULTS—C57BL/6 murine hearts were transplanted into B6.C-H2KhEg mice for examination of GAD. PD-L1 was expressed in SMCs of the thickened intima in the graft coronary arteries, and administration of anti–PD-L1 monoclonal antibody (mAb) enhanced the progression of GAD (luminal occlusion55±5.0% versus 9.8±4.3%, P
ISSN:	1079-5642 1524-4636
DOI:	10.1161/01.ATV.0000145015.23656.e4