Pre-activation of T lymphocytes by low dose of concanavalin A aggravates toll-like receptor-3 ligand-induced NK cell-mediated liver injury.
Concanavalin A (Con A), a widely used murine T cell stimulator, could induce T cell-mediated hepatitis when used in an abundant dosage. However, the immune-modulating role of non-hepatotoxic dosage of Con A in hepatic immune responses remains obscure. In order to evaluate the effect of non-hepatotoxic Con A on hepatic NK cells, pretreatment of mice with low dose of Con A was performed on polyinosinic-polycytidylic acid (poly I:C) [toll-like receptor-3 (TLR-3) ligand]-induced NK cell-mediated hepatitis. The role of the Con A-pre-activated T cells in NK cell function was then determined. The results demonstrated that Con A pretreatment aggravated poly I:C-induced liver injury with elevation of serum transaminases, hepatic necrosis and serum IFN-gamma level. In parallel to the enhanced accumulation of activated NK cells into liver, the natural cytotoxicity and IFN-gamma production by hepatic NK cells were significantly augmented. Moreover, depletion of T cells suppressed the aggravating effect of Con A pretreatment. Collectively, the aggravation of poly I:C-induced hepatitis by Con A pretreatment may be due to the generation of more vigorous NK cells which is dependent on the presence of T cells. This investigation will help to explain the synergistic effects of NK and T cells in liver inflammatory injury.
School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Jing
J
Wang
Rui
R
Sun
Haiming
H
Wei
Zhongjun
Z
Dong
Zhigang
Z
Tian
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008024:Ligands; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology
D000911:Antibodies, Monoclonal; D008024:Ligands; D051196:Toll-Like Receptor 3; D003208:Concanavalin A; D007371:Interferon-gamma; D011070:Poly I-C