Induction of antigraft and antirecipient antibody responses after fully allogeneic and semiallogeneic rat small bowel transplantation

Background. Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipie nt antibodies after allogeneic and semiallogeneic rat small bowel transplan tation. Methods. Fully allogeneic, unidirectional rejection and unidirectional graf t-versus-host disease (GVHD) heterotopic small bowel transplantation was pe rformed using DA, PVG, and (PVGxDA)F-1 donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by referenc e 60 a standard curve of fluorescent intensity generated using a serum samp le with known anti-target cell IgM activity. Data are presented as arbitrar y units/ml (AU/ml), Results. In the PVG-->DA combination, five of six DA recipients had detecta ble anti-graft (PVG;) antibodies by day 4 after transplantation (mean 72 AU /ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 day s in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses we re also induced in the DA-->PVG combination (day 6-218 AU/ml), however no a ntirecipient (PVG) response was apparent. Transplantation induced antirecip ient (DA) antibodies in the unidirectional GVHD model (day 6-90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6-6 0 AU/ml). However, the latter was quantitatively lower than that generated in the PVG-->DA combination (day 6-976 AU/ml). Conclusions. Antigraft and antirecipient antibody responses are simultaneou sly induced after fully allogeneic small bowel transplantation, despite rej ection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome.