title: Hepatocellular apoptosis associated with cytotoxic T/natural killer-cell infiltration in chronic active EBV infection.
abstract: The aim of the present study was to identify the mechanism of hepatocellular apoptosis induced by EBV-infected cytotoxic T/natural killer (NK) cells in chronic active EBV infection (CAEBV). Eight patients with CAEBV were studied, and infected T-cell expansion and NK-cell expansion were detected in four patients each. Biopsy or necropsy was performed on lymph node, liver, or spleen, and each specimen was subjected to immunohistochemical double staining of CD3 plus caspase-3 with the addition of cytotoxic markers of T-cell restricted intracellular antigen-1 (TIA-1), perforin, and granzyme B, as well as EBV in situ hybridization (EBV-ISH). In the liver, some of the infiltrating CD3-positive lymphocytes stained positively for EBV-ISH and cytotoxic markers. Double staining of CD3 plus caspase-3 indicated caspase-3 positive hepatocytes with apoptotic features, accompanied by extensive infiltration of CD3-positive cells, which were directly attached to the apoptotic caspase-3 positive hepatocytes. In contrast, far fewer cells stained positive for caspase-3 in lymph node and spleen than in liver. The present findings suggest that in patients with CAEBV, cytotoxic T/NK cells may directly induce hepatocytes to undergo apoptosis more frequently than they do cells in other organs of the reticulo-endothelial system.
authors: Department of Pathology, School of Medicine, Kurume University, Kurume, Japan. yuko-nomura@mvj.biglobe.ne.jp
authors: Yuko
authors: Y
authors: Nomura
authors: Hiroshi
authors: H
authors: Kimura
authors: Kennosuke
authors: K
authors: Karube
authors: Shiro
authors: S
authors: Yoshida
authors: Yasuo
authors: Y
authors: Sugita
authors: Daisuke
authors: D
authors: Niino
authors: Kei
authors: K
authors: Shimizu
authors: Yoshizo
authors: Y
authors: Kimura
authors: Ryosuke
authors: R
authors: Aoki
authors: Junichi
authors: J
authors: Kiyasu
authors: Masanori
authors: M
authors: Takeuchi
authors: Keiko
authors: K
authors: Hashikawa
authors: Shinichi
authors: S
authors: Hirose
authors: Koichi
authors: K
authors: Ohshima
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*