Bridging channel dendritic cells induce immunity to transfused red blood cells

Samuele Calabro, Antonia Gallman, Uthaman Gowthaman, Dong Liu, Pei Chen, Jingchun Liu, Jayendra Kumar Krishnaswamy, Manuela Sales L. Nascimento, Lan Xu, Seema R. Patel, Adam Williams, Christopher A. Tormey, Eldad A. Hod, Steven L. Spitalnik, James C. Zimring, Jeanne E. zHendrickson, Sean R. Stowell, Stephanie C. Eisenbarth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Red blood cell (RBC) transfusion is a life-saving therapeutic tool. However, a major complication in transfusion recipients is the generation of antibodies against non-ABO alloantigens on donor RBCs, potentially resulting in hemolysis and renal failure. Long-lived antibody responses typically require CD4+ T cell help and, in murine transfusion models, alloimmunization requires a spleen. Yet, it is not known how RBC-derived antigens are presented to naive T cells in the spleen. We sought to answer whether splenic dendritic cells (DCs) were essential for T cell priming to RBC alloantigens. Transient deletion of conventional DCs at the time of transfusion or splenic DC preactivation before RBC transfusion abrogated T and B cell responses to allogeneic RBCs, even though transfused RBCs persisted in the circulation for weeks. Although all splenic DCs phagocytosed RBCs and activated RBC-specific CD4+ T cells in vitro, only bridging channel 33D1+ DCs were required for alloimmunization in vivo. In contrast, deletion of XCR1+CD8+ DCs did not alter the immune response to RBCs. Our work suggests that blocking the function of one DC subset during a narrow window of time during RBC transfusion could potentially prevent the detrimental immune response that occurs in patients who require lifelong RBC transfusion support.

Original languageEnglish (US)
Pages (from-to)887-896
Number of pages10
JournalJournal of Experimental Medicine
Volume213
Issue number6
DOIs
StatePublished - May 30 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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