title: Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the liver.
abstract: Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired architectural disturbance that can lead to portal hypertension. Although frequently associated with autoimmune or hematologic malignancies, its exact pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the liver sinusoids of 14 of 44 NRH patients and explored possible relationships between these lymphocytes and vascular damage. The immunophenotype of intrahepatic lymphocytes was determined using immunohistochemical analysis and endothelial injury using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method for apoptosis combined with endothelial cell labeling. Controls for the quantitative analysis of liver-infiltrating lymphocytes consisted of patients with chronic hepatitis C or normal liver (n = 13 and n = 6, respectively). Liver specimens from the 14 patients dislayed intrasinusoidal infiltrate composed of CD3+ and CD8+ lymphocytes, located near atrophic liver cell plates. Significantly more granzyme B+ and CD57+ lymphocytes were observed in NRH than chronic hepatitis C samples with quantitatively similar CD8+ infiltrates. Double-labeling revealed apoptotic endothelial sinusoidal cells in CD8+ T-cell-infiltrated areas in all NRH samples but never in chronic hepatitis C or normal livers. T-cell receptor rearrangement or immunoscope analysis suggested liver-specific polyclonal or oligoclonal T-cell expansions. Clinical and biological characteristics of the 14 patients were similar to those observed in the 30 patients with NRH devoid of lymphocytic infiltration. We report here that CD8+ cytotoxic T cells infiltrated the liver sinusoids of a high percentage (32%) of NRH patients and suggest that some NRH cases might result from chronic, cytotoxic CD8+ T-lymphocyte targeting of sinusoidal endothelial cells.
authors.affiliation: UPRES-EA 3406, UFR SMBH Paris XIII University, Bobigny, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ziol
authors.forename: Helene
authors.initials: H
authors.lastname: Poirel
authors.forename: Gisele N
authors.initials: GN
authors.lastname: Kountchou
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Djamila
authors.initials: D
authors.lastname: Mohand
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Maryline
authors.initials: M
authors.lastname: Tepper
authors.forename: Jean-Gerard
authors.initials: JG
authors.lastname: Guillet
authors.forename: Catherine
authors.initials: C
authors.lastname: Guettier
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
mesh_terms: D000328:Adult; D000368:Aged; D001054:Apolipoproteins A; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000276:immunology* / Q000473:pathology; D015329:Gene Rearrangement, T-Lymphocyte; D006521:Hepatitis, Chronic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D001054:Apolipoproteins A