Format

Send to

Choose Destination
J Exp Med. 2016 May 30;213(6):887-96. doi: 10.1084/jem.20151720. Epub 2016 May 16.

Bridging channel dendritic cells induce immunity to transfused red blood cells.

Author information

1
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.
2
Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Yuexiu, Guangzhou, Guangdong, 510080, China.
3
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520.
4
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
5
Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
6
The Jackson Laboratory for Genomic Medicine, Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030.
7
Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, NY 10032.
8
Bloodworks NW Research Institute, University of Washington School of Medicine, Seattle, WA 98102 Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98102 Division of Hematology, Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA 98102.
9
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520 Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520.
10
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 stephanie.eisenbarth@yale.edu.

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.

PMID:
27185856
PMCID:
PMC4886363
DOI:
10.1084/jem.20151720
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center