Liver-infiltrating T lymphocytes cause hepatocyte damage by releasing humoral factors via LFA-1/ICAM-1 interaction in immunological liver injury.
OBJECTIVE
To explore the mechanisms by which liver-infiltrating T lymphocytes cause hepatocyte damage in the liver injury induced by delayed-type hypersensitivity to picryl chloride.


METHODS
Nonparenchymal cells (NPC) were isolated 12 h after liver injury elicitation and fractionated into Kupffer cell-enriched (Fr. A) and lymphocyte-enriched populations (Fr. B). They were used as the effectors for coculture with hepatocytes.


RESULTS
The cells in total NPC and Fr. B harvested at 12 h of liver injury were increased two- and six-fold respectively compared with those at 0 h. Fr. B, mainly including CD4+ and CD8+ T cells, exhibited a significantly stronger hepatotoxicity than total NPC did, while Fr.A did not. NPC at 12 h showed remarkably increased matrix metalloproteinase-2 and -9 activities indicative of infiltration potential through extracellular matrix. When NPC and hepatocytes were cultured in separated compartments in Transwell chamber, no hepatotoxicity was observed. However, 30 min-pre-contact with hepatocytes as stimulator significantly triggered NPC hepatotoxicity. The acquisition of such hepatotoxic potential was significantly abolished by anti-LFA-1 pretreatment for NPC or anti-ICAM-1 treatment for hepatocytes before contact. Both aprotonin and superoxide dismutase dose-dependently inhibited the hepatotoxicity.


CONCLUSIONS
Liver-infiltrating T lymphocytes may be triggered by hepatocytes via LFA-1/ICAM-1 interaction to release toxic substances, such as proteases and oxygen radicals, which consequently lead to the hepatocyte damage.
Xu
Q
Q
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China. qiangxu@jlonline.com
Cao
J S
JS
Zhang
X M
XM
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D013482:Superoxide Dismutase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9