Immunomodulation Based on a Two-Way Paradigm with Deoxyspergualin Alleviates Graft-versus-Host Reaction in Small-Bowel Transplantation in Rats

Abstract

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 pretreatment 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 postoperative 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 postoperative deoxyspergualin administration can lead to resistance to GVHR after parent-to-F1 small-bowel transplantation