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Transforming growth factor‐β released by apoptotic white blood cells during red blood cell storage promotes transfusion‐induced alloimmunomodulation
Author(s) -
Vallion Romain,
Bonnefoy Francis,
Daoui Anna,
Vieille Loredane,
Tiberghien Pierre,
Saas Philippe,
Perruche Sylvain
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13031
Subject(s) - apoptosis , immunology , flow cytometry , andrology , red blood cell , blood transfusion , medicine , leukoreduction , biology , biochemistry
BACKGROUND Red blood cell (RBC) alloimmunization is a major immunologic risk of transfusion. However, RBC storage facilitates white blood cell (WBC) apoptosis and apoptotic cells have immunomodulatory properties. We investigated the behavior of WBCs, and apoptosis in particular, in RBC units during storage and then studied the impact of WBC apoptosis on the modulation of posttransfusion alloimmunization in RBC products stored short term. STUDY DESIGN AND METHODS We used a mouse model of alloimmunization to transfused HEL‐ovalbumin‐Duffy (HOD) surface antigen expressed specifically on RBCs. The presence of circulating anti‐HOD immunoglobulin G detected by flow cytometry confirmed immunization to HOD+ RBCs. WBC apoptosis and factors released by apoptotic WBCs during storage were determined and in particular the role of transforming growth factor (TGF)‐β was assessed on RBC alloimmunization. RESULTS In blood stored 72 hours, 30% of WBCs were apoptotic, and transfusion of short‐term‐stored blood resulted in lesser immunization than did fresh blood or stored leukoreduced (LR) RBCs. WBCs undergoing apoptosis released during short‐term storage factors modulating RBC alloimmunization. Indeed apoptotic cell–released factors modulate alloimmunization whereas exogenous apoptotic cells directly transfused with LR RBCs did not. While microparticles released during RBC storage had no immunomodulatory role, TGF‐β found in the supernatant of stored blood demonstrated the capacity to favor Treg polarization of naïve CD4+CD25– T cells in vitro and limited RBC alloimmunization in vivo . Indeed, addition of recombinant TGF‐β to stored LR RBC transfusion strongly limited posttransfusion RBC alloimmunization. CONCLUSION Our findings show that short‐term storage of non‐LR blood facilitates WBC apoptosis therefore releasing TGF‐β that modulates posttransfusion RBC alloimmunization.