title: 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.
authors.affiliation: Établissement Français du Sang, Créteil, France Institut Mondor de Recherche Biomédicale, lnserm U955, Equipe 2, Créteil, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Rahma
authors.initials: R
authors.lastname: Elayeb
authors.affiliation: Établissement Français du Sang, Créteil, France Institut Mondor de Recherche Biomédicale, lnserm U955, Equipe 2, Créteil, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tamagne
authors.affiliation: Établissement Français du Sang, Créteil, France Institut Mondor de Recherche Biomédicale, lnserm U955, Equipe 2, Créteil, France Université Paris Est, Faculté de Médecine, Créteil, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.affiliation: Établissement Français du Sang, Créteil, France Institut Mondor de Recherche Biomédicale, lnserm U955, Equipe 2, Créteil, France Université Paris Est, Faculté de Médecine, Créteil, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Noizat-Pirenne
authors.affiliation: Établissement Français du Sang, Créteil, France Institut Mondor de Recherche Biomédicale, lnserm U955, Equipe 2, Créteil, France Laboratory of Excellence GR-Ex, Paris, France benoit.vingert@efs.sante.fr.
authors.forename: Benoît
authors.initials: B
authors.lastname: Vingert
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D056724:Immunity, Humoral; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D019076:Transgenes
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D010455:Peptides; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D018664:Interleukin-12; C421864:hen egg lysozyme; D009113:Muramidase; D011070:Poly I-C