Graft-versus-host reaction in small-bowel transplantation and possibilities for its circumvention

To study graft-versus-host reaction (GVHR) in small-bowel transplantation and its underlying mechanisms and to find methods for circumventing GVHR, we used an unidirectional GVHR model in which F₁ Lewis (LEW) × Wistar King A (WKA) hybrid rats received small-bowel transplants from either LEW or WKA parent rats. The survival time of F₁ hybrid rats that received full-length small-bowel transplantation from LEW and WKA was 16.3 ± 2.1 days and 18.2 ± 3.4 days, respectively. When one-quarter of LEW small bowel was transplanted to an F₁ hybrid recipient, the survival time was significantly longer at 44.0 ± 23.4 days compared with rats that had received full-length LEW small-bowel transplantation. The survival time of F₁ hybrid rats which received an injection of high-dose (5 × 10⁸ cells) LEW or WKA spleen cells was 11.9 ± 4.0 days and 13.1 ± 3.6 days, respectively. However, when an injection containing a low dose (1 × 10⁸ cells) of LEW spleen cells was used, survival was > 100 days, showing significance compared with the survival of rats receiving the higher dose LEW spleen-cell injection. Both small-bowel transplantation and spleen-cell injection were compared for the effective period of recipient resistance to donor cell or small-bowel transplantation as second challenge. When the F₁ rats given a quarter LEW small-bowel transplant as first challenge were treated with a high-dose of spleen cells 30 days after transplantation, they survived for > 30 days without GVHR. F₁ rats that were treated with a low-dose LEW spleen-cell injection, followed 30 days later by full LEW small-bowel transplantation, had a survival time of > 100 days. These results indicate that segmental small-bowel transplantation and spleen-cell injection as first challenge may facilitate the prevention of GVHR, resulting in resistance to subsequent immunological challenge.