Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells.
Factors regulating which patients become alloimmunized to red blood cell (RBC) antigens are poorly understood. Using a murine model of transfusion, we recently reported that viral-like inflammation with polyinosinic polycytidylic acid [poly (I:C)] significantly enhances RBC alloimmunization. Herein, we tested the hypothesis that poly (I:C) exerts this effect, at least in part, at the level of antigen-presenting cells (APCs). Using a novel in vivo method, we report that in the noninflamed state, most transfused RBCs were consumed by splenic macrophages, with only trace consumption by splenic dendritic cells (DCs). To a lesser extent, RBCs were also consumed by APCs in the liver. However, unlike soluble antigens, no RBCs were consumed by APCs in the lymph nodes. Inflammation with poly (I:C) induced significant consumption of transfused RBCs by splenic DCs, with a concomitant increase in costimulatory molecule expression. Moreover, this resulted in increased proliferation of CD4(+) T cells specific for the mHEL RBC alloantigen. Finally, splenectomy abrogated the enhancing effects of poly (I:C) on RBC alloimmunization. Together, these data provide additional insight into the nature of transfused RBCs as an immunogen and provide a mechanism by which viral-like inflammation enhances alloimmunization to transfused RBCs.
Hendrickson
Jeanne E
JE
Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Children's Healthcare of Atlanta, AFLAC Cancer Center and Blood Disorders Service, Atlanta, GA 30322, USA.
Chadwick
Traci E
TE
Roback
John D
JD
Hillyer
Christopher D
CD
Zimring
James C
JC
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000276:immunology*; D007114:Immunization; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D011070:Poly I-C