Specific immunosuppression by postoperative infusion of allogeneic spleen cells - Requirement of donor major histocompatibility complex expression and graft-versus-host reactivity

Background. Donor leukocytes may exert positive immunoregulatory effects on allograft acceptance. Most recent studies have focused on pretreatment pro tocols. In this study, the effect of postoperative infusion of donor leukoc ytes on graft survival and the phenotypic and functional requirements for i nfused cells were investigated in fully major histocompatibility complex (M HC)-mismatched rat heart transplant models. Methods. LEW (RT1(1)) heart grafts were implanted heterotopically into abdo mens of LEW.1W (RT1(u)), and different types of cells were infused postoper atively. Immunohistochemistry was used to evaluate histopathological change s of grafts. Results. In the absence of any immunosuppressive agents, a single dose of v iable donor spleen cells (SC), but not bone marrow cells, was able to prolo ng heart allograft survival to about 21 days, while they were rejected prom ptly at day 7 in controls. Infusion of T cell-depleted donor SC, irradiated donor SC or third-party (BN) SC showed no effect on graft survival. Compar ed with resting cells, neither in vitro nor in vivo prestimulation of infus ed donor SC improved graft survival. Clinical signs of graft-versus-host re action were not observed in all above groups. Histology showed remarkable r eduction in the severity of graft infiltrate and interleukin-2 receptor-pos itive cells in grafts of cell-treated animals. Postoperative infusion of SC of F1 generation between different strain combinations showed two requirem ents for infused cells to be effective: (1) expression of donor-type MHC an tigens and (2) strong alloreactivity against the host MHC antigens, Conclusion. Postoperative infusion of viable donor SC can lead to allospeci fic down-regulation of alloreactivity by a graft-versus-host-associated eff ect.