Immunomodulation based on a two-way paradigm with deoxyspergualin alleviates graft-versus-host reaction in small-bowel transplantation in rats

In this study, we investigated whether or not deoxyspergualin used as donor pretreatment, with and without pretreatment using bone-marrow-cell injection, could alleviate graft-versus-host reaction (GVHR) following small-bowel transplantation in an unidirectional GVHR model with Lewis (LEW)-to-F₁ rats. In addition, we studied the effect of deoxyspergualin plus bone-marrow-cell donor pre-operative treatment in combination with recipient post-operative treatment using deoxyspergualin. When the donor was pretreated with bone-marrow cells from recipient rats, the recipient died at 7.2 ± 1.4 days, showing significantly shorter survival compared with the control group. Deoxyspergualin, when employed either alone as recipient post-treatment or as donor pretreatment, both with and without additional pre-treatment with F₁ recipient bone-marrow-cell injection, did not result in significant prolongation of recipient survival. The combination of donor pretreatment with deoxyspergualin plus F₁ bone-marrow-cell injection followed by post-operative deoxyspergualin administration, however, resulted in significant prolongation in recipient survival compared with control (26.1 ± 1.7 days). In addition, no severe cutaneous lesions on GVHR were seen throughout the observation period. This suggests that donor pretreatment with deoxyspergualin and recipient bone-marrow-cell injection combined with post-operative deoxyspergualin administration can lead to resistance to GVHR after parent-to-F₁ small-bowel transplantation.