Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat

Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1¹) or BN (RT1(n)) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F₁ hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F₁ combination, but was much less frequent in BN-into-F₁ SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F₁ combination. In MLR, hepatic T-cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F₁ hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting.