title: Lobular damage caused by cellular and humoral immunity in liver allograft rejection.
abstract: BACKGROUND
  Diagnosis of acute liver allograft rejection (ALAR) is usually performed by the estimation of changes in portal areas. In this study, changes in the hepatic lobules were investigated retrospectively by immunohistochemistry, and compared with changes in the portal areas. Humoral immunity in ALAR was also studied by C4d-staining.
  
  
  METHODS
  In total, 35 biopsy specimens from 20 patients who had undergone living-related liver transplantation were included. Specimens had been graded as mild, moderate-to-severe acute rejection based on the Banff Schema. Changes in hepatic lobules were investigated by hematoxylin-eosin (H & E) staining, an immunohistochemical study using anti-CD3 (T cells), anti-GMP-17 (cytotoxic cells), anti-CD68 (macrophages) and C4d, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method.
  
  
  RESULTS
  Changes in hepatic lobules consisted of the infiltration of mononuclear cells, swelling and necrosis of hepatocytes, and hemorrhages. The degree of these changes increased with the severity of ALAR. Immunohistochemical analysis revealed that infiltrating cells included CD3+ T cells, GMP-17+ cytotoxic cells and CD68+ macrophages. The number of infiltrating cells increased with the severity of the ALAR. The TUNEL assay demonstrated apoptotic cells in ALAR and the number of apoptotic cells increased with the severity of the ALAR. In moderate-to-severe rejection, C4d depositions were observed in the hepatic sinusoids as well as the portal veins and hepatic arteries.
  
  
  CONCLUSIONS
  Changes in the hepatic lobules were observed in ALAR and the severity increased with the severity of ALAR. Apoptosis was involved in the mechanism of cell death and humoral immunity plays a role in the mechanism of ALAR.
authors.affiliation: Second Department of Surgery, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. tsawada@dokkyomed.ac.jp
authors.forename: Tokihiko
authors.initials: T
authors.lastname: Sawada
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
authors.forename: Shohei
authors.initials: S
authors.lastname: Fuchinoue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teraoka
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007150:Immunohistochemistry; D007223:Infant; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D012189:Retrospective Studies; D013194:Staining and Labeling
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d