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 injecti on, could alleviate graft-versus-host reaction (GVHR) following small-bowel transplantation in an unidirectional GVHR model with Lewis (LEM)-to-F-1 ra ts. In addition, we studied the effect of deoxyspergualin plus bone-marrow- cell donor pre-operative treatment in combination with recipient post-opera tive treatment using deoxyspergualin. When the donor was pretreated with bo ne-marrow cells from recipient rats, the recipient died at 7.2 +/- 1.4 days , showing significantly shorter survival compared with the control group. D eoxyspergualin, when employed either alone as recipient post-treatment or a s donor pretreatment, both with and without additional pretreatment with F- 1 recipient bone-marrow-cell injection, did not result. in significant prol ongation of recipient survival. The combination of donor pretreatment with deoxyspergualin plus F-1 bone-marrow-cell injection followed by post-operat ive deoxyspergualin administration, however, resulted in significant prolon gation in recipient survival compared with control (26.1 +/- 1.7 days). In addition, no severe cutaneous lesions on GVHR were seen throughout the obse rvation period. This suggests that donor pretreatment deoxyspergualin and r ecipient bone-marrow-cell injection combined with postoperative deoxyspergu alin administration can lead to resistance to GVHR after parent-to-F-1 smal l-bowel transplantation.