Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.