Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model

Background. Lymphoid tissue within the intestinal graft require immunomodul atory strategies to prevent graft versus host disease (GVHD) after transpla nt. Herein, we evaluate the potential advantage of donor-specific bone marr ow infusions in donor and or recipient preconditioned with total body irrad iation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejec tion after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distribut ed in nine groups: control group GO (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n =6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G 6 were given 250 rd of total body irradiation 2 hours before intestinal ret rieval. Donors and recipients in G7 and donors in GS additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with t he same amount of TCDBM. Animals received tacrolimus for 15 days and access ed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2,3, and 4, and correl ated with high levels of donor T cells in recipients blood. GO and G1 showe d early acute rejection with progression toward chronic rejection, in contr ast to the preconditioned groups. High and low doses of total body irradiat ion resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correl ated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with reci pient preconditioning and donor-specific bone marrow infusions prevented GV HD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.