Intrahepatic expression of the co-stimulatory molecules programmed death-1, and its ligands in autoimmune liver disease.
Liver-infiltrating T cells play an essential role in the immunopathogenesis of autoimmune liver disease. Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that are involved in the regulation of immune responses. The ligation of PD-1 inhibits T-cell receptor-mediated T cell proliferation and cytokine production, and PD-1-deficient mice develop various organ-specific autoimmune diseases. To investigate the expressions of PD-1 and its ligands in autoimmune liver disease, in particular autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), immunohistochemical analysis was performed. Liver biopsy specimens obtained from 17 patients with AIH and PBC were studied. PD-1 was expressed on more than half of the liver-infiltrating T cells within the portal tract. Some of the intrahepatic T cells expressed B7-H1 in patients with AIH and PBC. B7-H1 and B7-DC were mainly expressed on some Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC) within the sinusoids and their expression was upregulated in autoimmune liver disease. These results suggest that the interaction of PD-1 on T cells with increased expression of B7-H1 and B7-DC on KC and LSEC might be involved in the downregulation of autoreactive lymphocytes and result in the regulation of pathogenesis in autoimmune liver disease.
Oikawa
Tsunekazu
T
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Takahashi
Hiroki
H
Ishikawa
Tomohisa
T
Hokari
Atsushi
A
Otsuki
Noriko
N
Azuma
Miyuki
M
Zeniya
Mikio
M
Tajiri
Hisao
H
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D008024:Ligands; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor