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

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.

• Authors: 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 Hendrickson, Sean R Stowell, Stephanie C Eisenbarth
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 213 Issue 6 Pg. 887-96 (05 30 2016) ISSN: 1540-9538 [Electronic] United States
• PMID: 27185856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Calabro et al.

Chemical References

• ABO Blood-Group System
• Abo protein, mouse
• Galactosyltransferases

Topics

• ABO Blood-Group System (genetics, immunology)
• Animals
• B-Lymphocytes (immunology, pathology)
• Dendritic Cells (immunology)
• Erythrocyte Transfusion
• Galactosyltransferases (genetics, immunology)
• Mice
• Mice, Transgenic
• Phagocytosis (immunology)
• Spleen (immunology, pathology)
• T-Lymphocytes (immunology, pathology)