TY - JOUR
T1 - Bridging channel dendritic cells induce immunity to transfused red blood cells
AU - Calabro, Samuele
AU - Gallman, Antonia
AU - Gowthaman, Uthaman
AU - Liu, Dong
AU - Chen, Pei
AU - Liu, Jingchun
AU - Krishnaswamy, Jayendra Kumar
AU - Nascimento, Manuela Sales L.
AU - Xu, Lan
AU - Patel, Seema R.
AU - Williams, Adam
AU - Tormey, Christopher A.
AU - Hod, Eldad A.
AU - Spitalnik, Steven L.
AU - Zimring, James C.
AU - zHendrickson, Jeanne E.
AU - Stowell, Sean R.
AU - Eisenbarth, Stephanie C.
N1 - Publisher Copyright:
© 2016 Calabro et al.
PY - 2016/5/30
Y1 - 2016/5/30
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20151720
DO - 10.1084/jem.20151720
M3 - Article
C2 - 27185856
AN - SCOPUS:84971572057
SN - 0022-1007
VL - 213
SP - 887
EP - 896
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -