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

Abstract

Donor leukocytes may exert positive immunoregulatory effects on allograft acceptance. Most recent studies have focused on pretreatment protocols. In this study, the effect of postoperative infusion of donor leukocytes on graft survival and the phenotypic and functional requirements for infused cells were investigated in fully major histocompatibility complex (MHC)-mismatched rat heart transplant models. LEW (RT1l) heart grafts were implanted heterotopically into abdomens of LEW.1W (RT1u), and different types of cells were infused postoperatively. Immunohistochemistry was used to evaluate histopathological changes of grafts. In the absence of any immunosuppressive agents, a single dose of viable donor spleen cells (SC), but not bone marrow cells, was able to prolong heart allograft survival to about 21 days, while they were rejected promptly 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. Compared with resting cells, neither in vitro nor in vivo prestimulation of infused donor SC improved graft survival. Clinical signs of graft-versus-host reaction were not observed in all above groups. Histology showed remarkable reduction in the severity of graft infiltrate and interleukin-2 receptor-positive cells in grafts of cell-treated animals. Postoperative infusion of SC of F1 generation between different strain combinations showed two requirements for infused cells to be effective: (1) expression of donor-type MHC antigens and (2) strong alloreactivity against the host MHC antigens. Postoperative infusion of viable donor SC can lead to allospecific down-regulation of alloreactivity by a graft-versus-host-associated effect.