Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs

Blood. 2012 Feb 9;119(6):1566-9. doi: 10.1182/blood-2011-09-382655. Epub 2011 Nov 10.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Antibodies / blood
  • Antibodies / immunology
  • Antigens / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocyte Transfusion / methods*
  • Erythrocytes / immunology*
  • Erythrocytes / metabolism
  • Female
  • Glycophorins / genetics
  • Glycophorins / immunology
  • Humans
  • Immune Tolerance / immunology*
  • Inflammation / blood
  • Inflammation / immunology*
  • Isoantibodies / blood
  • Isoantibodies / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muramidase / genetics
  • Muramidase / immunology

Substances

  • Antibodies
  • Antigens
  • Glycophorins
  • Isoantibodies
  • hen egg lysozyme
  • Muramidase