Kinetics and localization of lymphoblasts that proliferate in the murine liver after concanavalin a administration

Concanavalin A (Con A) induces T cell-dependent hepatic injury in mite. In order to demonstrate intrahepatic activation and proliferation of T cells and its relationship with hepatic injury, we examined the kinetics and distribution of infiltrating lymphocytes in the murine liver after Con A administration. Small lymphocytes began to increase in the hepatic sinusoid at 1 h and migrate extrasinusoidally at 8 h. Confluent necrosis of hepatocytes occurred at 8 h, but there was no obvious association of lymphocytes with the necrotic foci. Many lymphoblasts appeared at 16 h and were accumulated in the space of Disse and portal tracts where they underwent proliferation at 16-24 h. They were also accumulated around the necrotic foci at 24-48 h. Con A-treated rat liver and anti-CD3 antibody-treated mouse liver exhibited intrahepatic accumulation of lymphoblasts without liver injury. The present study has revealed that in vivo T cell activation by Con A induces intrahepatic proliferation and accumulation of lymphoblasts particularly in the extravascular compartments like the space of Disse and portal tracts, but extrasinusoidal migration of Con A-activated lymphocytes itself may not give direct cytotoxic effects on hepatocytes.