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Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

Abstract : Murine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization. In vaccination studies, the intensity of antigen-specific responses depends on the delay between antigen and adjuvant administration, with a short delay limiting immune responses. In mouse models of alloimmunization, the delay between the injection of Toll-like receptor agonists and transfusion is usually short. In this study, we hypothesized that the timing of Toll-like receptor 3 agonist administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like receptor 3 agonist, was administered to B10BR mice at various time points before the transfusion of HEL-expressing red blood cells. For each time point, we measured the activation of splenic HEL-presenting dendritic cells, HEL-specific CD4(+) T cells and anti-HEL antibodies in serum. The phenotype of activated immune cells depended on the delay between transfusion and Toll-like receptor-dependent inflammation. The production of anti-HEL antibodies was highest when transfusion occurred 7 days after agonist injection. The proportion of HEL-presenting CD8α(+) dendritic cells producing interleukin-12 was highest in mice injected with poly(I:C) 3 days before transfusion. Although the number of early-induced HEL-specific CD4(+) T cells was similar between groups, a high proportion of these cells expressed CD134, CD40 and CD44 in mice injected with poly(I:C) 7 days before transfusion. This study clearly shows that the delay between transfusion and Toll-like receptor-induced inflammation influences the immune response to transfused red blood cells.
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https://www.hal.inserm.fr/inserm-03129775
Contributor : Benoit Vingert <>
Submitted on : Wednesday, February 3, 2021 - 9:41:21 AM
Last modification on : Thursday, February 4, 2021 - 3:26:48 AM
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Rahma Elayeb, Marie Tamagne, Philippe Bierling, F Noizat-Pirenne, Benoît Vingert. Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion. Haematologica, Ferrata Storti Foundation, 2015, 101, pp.209 - 218. ⟨10.3324/haematol.2015.134171⟩. ⟨inserm-03129775⟩

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