Figure 2. Alloimmunity initiated by hepatocellular transplantation directly (intraportal injection) to the liver induces high magnitude and persistent CD8-medated in vivo allocytotoxicity.
FVB/N hepatocytes (H-2q) were injected into untreated wild-type hosts (WT; H-2b) by intraportal injection or by intrasplenic injection. A) Allospecific in vivo cytotoxic effector activity was measured serially following transplantation, in both recipient groups. Both groups developed high magnitude cytotoxicity by 7 days posttransplant (intraportal=87±4%, intrasplenic=90±2%), but intraportal injection uniquely resulted in sustained cytotoxic activity beyond the time of graft rejection (day 14=93±3%, day 21=90±4%, day 35=72±13%), whereas recipients receiving intrasplenic injection showed a sharp decrease in cytotoxicity following graft rejection (day 14=26±4%, day 21=16±6%, day 35=7±2%; p<0.01 for all time points, signified by “*”). Each data point represents n=4–6 animals per time point. B) CD8+ T cell depletion using monoclonal antibodies on days 6 and 7 posttransplant, 48 hours prior to the in vivo cytotoxicity assay (day 7 posttransplant), eliminated the cytotoxic effector function in hepatocyte recipients (6±2%; p<0.001, signified by “*”; n=4) demonstrating that in vivo effector function in hepatocyte recipients is CD8-mediated. The error bars represent standard error.