Protective role of γδ T cells in concanavalin A-induced liver injury / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role played by γ&delta; T cells in acute liver injury using the concanavalin A (ConA)-induced liver injury mouse model.</p><p><b>METHODS</b>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 &delta;-/-) 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 γ&delta; T cells and proportions of different subsets in liver lymphocytes were measured by flow cytometry.</p><p><b>RESULTS</b>The TCR &delta;-/- 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 γ&delta; T cells increased with increased injury degree, and the extent of increase was significantly higher in the TCR &delta;-/- 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 γ&delta; T cells to total γ&delta; 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 γ&delta; T cells to total γ&delta; 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 γ&delta; T lymphocytes into TCR &delta;-/- mice led to lower serum ALT levels than reinfusion of Vγ1 γ&delta; T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L).</p><p><b>CONCLUSION</b>γ&delta; T cells play a protective role in ConA-induced liver injury and this effect maybe mediated by the Vγ4 γ&delta; T cell subset.</p>