[Protective role of γδ T cells in concanavalin A-induced liver injury].
OBJECTIVE
To investigate the role played by γδ T cells in acute liver injury using the concanavalin A (ConA)-induced liver injury mouse model.


METHODS
Acute liver injury was induced by intravenous injection of 10 mug/g of ConA into male C57BL/6J mice with wild-type or T cell receptor-γ knockout (TCR δ-/-) genetic backgrounds. Mice injected with PBS alone served as negative controls. The degree of liver damage was assessed by measuring serum levels of transaminase and cytokines at post-injection hours 3, 6, 12, 24, 48, and 72. The percentage of γδ T cells and proportions of different subsets in liver lymphocytes were measured by flow cytometry.


RESULTS
The TCR δ-/- mice showed significantly higher levels of the inflammatory cytokines IFN-γ, TNFα and IL-4 than the wild-type mice at post-injection hour 3. The percentage of liver γδ T cells increased with increased injury degree, and the extent of increase was significantly higher in the TCR δ-/- mice than the wild-type mice (post-injection hour 6: 6302.61+/-592.06 vs. 1319.26+/-355.48, 12: 6569.44+/-1060.98 vs. 3415.53+/-343.90, 24: 6514.29+/-757.26 vs. 2062.73+/-365.67, 48: 1262.61+/-558.07 vs. 113.66+/-113.26, and 72: 226.54+/-98.20 vs. 42.35+/-21.51 U/L; all P less than 0.05). In addition, compared to the negative control mice, the ConA-induced mice showed a higher proportions of Vγ4 γδ T cells to total γδ T cells (17.78+/-2.95 vs. 25.26+/-2.43) and to total liver lymphocytes (0.47+/-0.07 vs. 0.66+/-0.05). Similarly, compared to the negative control mice, the ConA-induced mice showed a higher proportion of Vγ1 γδ T cells to total γδ T cells (38.37+/-6.10 vs. 50.19+/-5.52) but the proportion to total liver lymphocytes was not significantly different among the groups (0.76+/-0.18 vs. 0.78+/-0.25). Reinfusion of Vγ4 γδ T lymphocytes into TCR δ-/- mice led to lower serum ALT levels than reinfusion of Vγ1 γδ T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L).


CONCLUSIONS
γδ T cells play a protective role in ConA-induced liver injury and this effect maybe mediated by the Vγ4 γδ T cell subset.
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Na
N
Zhao
Yuanyuan
Y
Ni
Liqing
L
Zhao
Zhenzhou
Z
Wu
Zhinan
Z
Yin
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma