Poly I:C prevents T cell-mediated hepatitis via an NK-dependent mechanism.
OBJECTIVE
T cell immune responses play key roles in the pathogenesis of viral hepatitis, and innate immunity is known to be also activated during this process, however, the effects of innate immunity activation on T cell-mediated hepatitis remain obscure. Here we examined the effect of the activation of NK cells induced by toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly I:C), on concanavalin A (Con A)-induced T cell-mediated liver injury.


METHODS
Mice received nontoxic intraperitoneal poly I:C injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the function of hepatic lymphocytes was detected by FACS analysis.


RESULTS
Poly I:C pretreatment protected against T cell-mediated hepatitis, as evidenced by decreased mortality, hepatic necrosis, serum transaminase levels and inflammatory cytokines (IL-4, IFN-gamma). The protective effect of poly I:C was diminished in NK-depleted mice, which could be partially restored by adoptive transfer of NK cells. Administration of poly I:C caused NKT and T cell apoptosis via enhancing expression of Fas protein on these cells and expression of Fas ligand on NK cells.


CONCLUSIONS
These findings suggest that activation of NK cells by poly I:C prevents Con A-induced T cell-hepatitis via downregulation of T/NKT cells and subsequent reduction of inflammatory cytokines.
Wang
Jing
J
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Sun
Rui
R
Wei
Haiming
H
Dong
Zhongjun
Z
Gao
Bin
B
Tian
Zhigang
Z
D000818:Animals; D017209:Apoptosis; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006505:Hepatitis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007369:Interferon Inducers / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000008:administration & dosage / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000637:Transaminases / Q000097:blood
D007369:Interferon Inducers; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma; D000637:Transaminases; D011070:Poly I-C