ESTABLISHMENT OF A T-CELL-DEPENDENT NUDE-MOUSE LIVER-INJURY MODEL INDUCED BY PROPIONIBACTERIUM-ACNES AND LPS

Normal ICR mice developed severe liver injury when they were given intravenous injections of Propionibacterium acnes and lipopolysaccharide (LPS) with a 7 day interval. In contrast, T cell-deficient ICR nude mice were resistant to P. acnes and LPS-induced liver injury. However, athymic ICR nude mice, which were treated with cell transfer of normal ICR mouse spleen cells (10(8) cells) or ICR mouse nylon-wool passed splenic T-enriched cells (over 10(7) cells), showed severe liver injury as assessed by elevation of serum transaminase activities. Histological analyses also demonstrated that the transferred cells migrated into the liver of nude mice to induce liver injury. However, depletion of both CD4(+) T cells and CD8(+) T cells from transferred cell populations caused a marked decrease in the elevation of serum transaminase, indicating the actual involvement of T cells in liver injury. Moreover, in vivo administration of anti-LFA-1 mAb blocked P. acnes and LPS-induced liver injury in nude mice following T cell transfer. Thus, this model will provide a new strategy to investigate T cell-dependent cell-cell interaction during the induction of liver damage.