title: Semi-allogeneic (F1) versus fully allogeneic blood transfusions: differences in their ability to induce specific immunological unresponsiveness.
abstract: The beneficial effect on graft survival achieved by pretransplant blood transfusions is well established. However, the type of major histocompatibility complex (MHC) mismatch between transfusion donor and recipient seems to play a role in determining the outcome. The hypothesis that this sharing of MHC antigens is correlated with the level of sensitization or tolerization was studied in mice by pretreatment with semi-allogeneic (F1) or with fully allogeneic whole blood transfusions. Limiting dilution analysis (LDA) in vitro for donor-specific T helper (Thp) and cytotoxic T lymphocyte precursors (CTLp) performed on splenocytes isolated from transfused recipients 2 or 4 weeks after transfusion showed that the duration and magnitude of the response was reduced after a semi-allogeneic compared to a fully allogeneic transfusion. After a semi-allogeneic transfusion, both Thp and CTLp frequencies had returned to naive levels 4 weeks after transfusion, whereas after infusion of fully allogeneic blood, they remained elevated after 4 weeks. When a fully allogeneic heart was transplanted 2 or 4 weeks after transfusion, a small but significant improvement in graft prolongation (2 weeks, not significant, 4 weeks: p < 0.01) was observed following pretreatment with a semi-allogeneic transfusion (2 weeks: median survival time (MST) 30 days, 4 weeks: MST 29 days) compared to that obtained after fully allogeneic transfusion (2 weeks: MST 23 days, 4 weeks: MST 12 days). The semi-allogeneic transfusions were correlated with a statistically significant prolonged (7 days) persistence of donor-derived MHC class II+ cells in the recipient and with reduced levels of anti-donor MHC class I-specific antibody formation compared to these responses after transfusion with fully allogeneic cells. These results demonstrate that pretreatment with a semi-allogeneic blood transfusion is more tolerizing and less sensitizing than pretreatment with a fully allogeneic blood transfusion. These findings may be explained by the sharing of MHC antigens between recipient and transfusion donor.
authors.affiliation: University of Oxford, Nuffield Department of Surgery, John Radcliffe Hospital, Headington, GB. Droelen@surgery.oxford.ac.uk
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: E L
authors.initials: EL
authors.lastname: Dover
authors.forename: M
authors.initials: M
authors.lastname: Niimi
authors.forename: N T
authors.initials: NT
authors.lastname: Young
authors.forename: P J
authors.initials: PJ
authors.lastname: Morris
authors.forename: K J
authors.initials: KJ
authors.lastname: Wood
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001782:Blood Donors; D001803:Blood Transfusion; D006082:Graft Enhancement, Immunologic; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007519:Isoantigens / Q000276:immunology*; D016399:Lymphoma, T-Cell; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured
chemical_list: D007519:Isoantigens