Lack of graft-versus-host disease after fetal intestine transplantation

Abstract

Clinical small bowel transplantation has often been complicated by lethal graft-versus-host disease (GVHD), attributed to the numerous allogeneic immunocompetent lymphocytes contained in the graft. Because the fetal immune system is relatively immature, the authors hypothesized that the risk of GVHD after small bowel transplantation might be diminished by using the fetal intestine as the donor organ. This experiment tested this hypotheses in a rat model. Jejunoileal segments harvested from Lewis (LEW) rat fetuses were transplanted subcutaneously into adult recipients of either syngeneic LEW or semiallogeneic LEW × Brown-Norway F1 (LBNF1) strains. The recipients had follow-up for 21 days after transplantation to assess the growth of the intestinal grafts (“neogut”) and evaluate for GVHD. Growth of the intestinal grafts was observed in 65% (53 of 82) of the recipients, with a neogut weight of 4.5 ± 3.7 g and length of 2.8 ± 2.1 cm. No significant difference in graft survival rate or neogut weight and length was found between the LEW and LBNF1 recipients. Histopathologic examination of the neogut showed a mature intestinal architecture similar to that of normal adult rat intestine, with well-developed enteric lymphoid tissues including Peyer's patches. However, no clinical or histopathologic evidence of GVHD was found in any of the LBNF1 recipients. These results are consistent with the authors' hypothesis and suggest that the use of fetal donor intestine for small bowel transplantation might have some immunologic advantages over the adult (immunologically mature) donor intestine.