title: Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs.
abstract: Most human transfusion recipients fail to make detectable alloantibodies to foreign RBC antigens ("nonresponders"). Herein, we use a murine model to test the hypothesis that nonresponders may be immunologically tolerant. FVB mice transfused with RBCs expressing transgenic human glycophorin A (hGPA) antigen in the absence of inflammation produced undetectable levels of anti-hGPA immunoglobulins, unlike those transfused in the presence of polyinosinic:polycytidylic acid-induced inflammation. Mice in the nonresponder group failed to produce anti-hGPA after subsequent transfusions in the presence of polyinosinic:polycytidylic acid, whereas anti-hGPA levels increased in the responder group. This tolerance was antigen specific, because nonresponders to hGPA produced alloantibodies to RBCs that expressed a different transgenic antigen. This tolerance was not an idiosyncrasy of the hGPA antigen nor of the recipient strain, because B10.BR mice transfused with membrane-bound hen egg lysozyme antigen-transgenic RBCs also demonstrated induced nonresponsiveness. These data demonstrate that RBCs transfused in the absence of inflammation can induce tolerance.
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Smith
authors.forename: Eldad A
authors.initials: EA
authors.lastname: Hod
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Hendrickson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000941:Antigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D017707:Erythrocyte Transfusion / Q000379:methods*; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006021:Glycophorins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D006021:Glycophorins; D007518:Isoantibodies; C421864:hen egg lysozyme; D009113:Muramidase
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