Submitted March 30, 2007
Accepted June 22, 2007
Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells
Jeanne E Hendrickson, Traci E Chadwick, John D Roback, Christopher D Hillyer, and James C Zimring*
Dept of Pediatric Hematology/Oncology, Emory Univ School of Med., Children's Healthcare of Atlanta, AFLAC Cancer Ctr & Blood Disorders Serv, Atlanta, GA, United States
Department of Pathology & Laboratory Medicine, Center for Transfusion & Cellular Therapies, Emory University School of Medicine, Atlanta, GA, United States
* Corresponding author; email: jzimrin{at}emory.edu.
Factors regulating which patients become alloimmunized to RBC antigens are poorly understood. Using a murine model of transfusion, we recently reported that viral-like inflammation with 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. Using a novel in vivo method, we report that in the non-inflamed state, the majority of transfused RBCs were consumed by splenic macrophages, with only trace consumption by splenic dendritic cells. To a lesser extent, RBCs were also consumed by antigen presenting cells in the liver. However, unlike soluble antigens, no RBCs were consumed by antigen presenting cells in the lymph nodes. Inflammation with poly (I:C) induced significant consumption of transfused RBCs by splenic dendritic cells, with a concomitant increase in co-stimulatory 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.
