Fetal intestinal transplant model for mucosal immune responses

A rat fetal intestinal transplant model was developed for long-term study of intestinal immune responses. For the model, fetal small intestine is transplanted into the dorsal subcutaneous tissue of syngeneic adults and allowed to mature, providing an accessible site, isolated from the intestinal stream. We previously demonstrated normal histologic maturation of the transplant. Specific antibody-producing cells appeared in the lamina propria of both transplant and native in situ intestine following intraluminal immunization of the transplant with cholera toxin, and conversely, in transplants after immunization of in situ intestine. An enterointestinal lymphocyte migratory pathway (originating in intestine and migrating to another region of the intestine) was thus demonstrated unequivocally. We found a bacterial flora in the transplant, and showed normal villus morphology in scanning electron microscopy. Less than 200 pg, i.e., a 10(-7) fraction, of 2 mg macromolecular lipopolysaccharide placed in the transplant lumen was absorbed per plasma lipopolysaccharide half-life. Immunization of the transplant with cholera toxin resulted in specific IgA and IgG antibody in the transplant lumen and in bile, and specific IgG, but not IgA, antibody in serum. A second dose of antigen gave an anamnestic rise in intra-transplant antibody. Intestinal immune tolerance was also demonstrated: sheep red blood cells (SRBC) administered into the transplant for 7 days suppressed splenic IgM plaque forming responses to subsequent intraperitoneal challenge with SRBC. These studies further demonstrate that the fetal intestinal transplant behaves immunologically like native intestine, and therefore provides a useful model for investigation of the intestinal immune system.