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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2736-2743. Prepublished online as a Blood First Edition Paper on June 25, 2007; DOI 10.1182/blood-2007-03-083105. This Article Full Text (PDF) All Versions of this Article: blood-2007-03-083105v1 110/7/2736    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hendrickson, J. E Articles by Zimring, J. C Search for Related Content PubMed PubMed Citation Articles by Hendrickson, J. E Articles by Zimring, J. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Higgins and S. R. Sloan Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders Blood, September 15, 2008; 112(6): 2546 - 2553. [Abstract] [Full Text] [PDF] D. Brinc, H. Le-Tien, A. R. Crow, V. Siragam, J. Freedman, and A. H. Lazarus Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model J. Immunol., July 15, 2008; 181(2): 948 - 953. [Abstract] [Full Text] [PDF]

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