Combined liver-spleen-small intestine grafting in a rat model: role of transplanting additional lymphoid tissue on survival

The aim of this study was to develop suitable models of combined intestinal grafting to examine the enhancing effect of intestinal grafting with additional lymphoid tissue using 30% of the liver mass and the whole spleen on recipient survival in the absence of immunosuppression. Grafts from DA (RT1a) rats were transplanted orthotopically to PVG (RT1(1)) recipients according to the following design: group 1 (n = 6), en bloc 30% liver/entire SB/spleen; group 2 (n = 7), en bloc 30% liver/SB; group 3 (n = 7), SB/spleen and group 4 (n = 7), SB control for the preceding groups. The orthotopic nature and proximal interposition of the SB graft allowed the assessment of protection afforded by components of the cluster on the SB graft using survival endpoints. Although group 4 hosts survived half as long compared to other groups, statistical significance was reached only in the case of group 1; group 1 MST equalled 15.3 days, significantly higher than group 4 (p = 0.01). Acute rejection was present in every grafted tissue and was equivalent whether liver was included or excluded in the cluster. GVHD was absent postoperatively using clinical or histological criteria; recipient spleens showed hyperplasia, donor spleens depicted lymphocytic depletion on histology. This study determined that statistically proven enhanced survival was obtained only after grafting 30% liver plus spleen with the entire SB. GVHD was rare in the fully allogeneic system despite transplanting a massive load of lymphoid tissue. The surgical models used in this study employing liver in the cluster, address the important question of how best to evaluate the role of heterotopic accessory liver grafting in providing tolerance to co-transplanted small intestine.