Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells

Author:

Hendrickson Jeanne E.12,Chadwick Traci E.2,Roback John D.2,Hillyer Christopher D.12,Zimring James C.2

Affiliation:

1. Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Children's Healthcare of Atlanta, AFLAC Cancer Center and Blood Disorders Service, Atlanta, GA;

2. Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference47 articles.

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3. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion.;Heddle;Br J Haematol,1995

4. Multiple red cell transfusions and alloimmunization: experience with 6996 antibodies detected in a total of 159,262 patients from 1985 to 1993.;Hoeltge;Arch Pathol Lab Med,1995

5. A prospective study of the incidence of red cell allo-immunisation following transfusion.;Redman;Vox Sang,1996

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