Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion
Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion
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DOI：
10.3324/haematol.2015.134171
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发表时间：
2016-02-01
期刊：
影响因子：
10.1
通讯作者：
Vingert, Benoit
中科院分区：
文献类型：
--
作者：
Elayeb, Rahma;Tamagne, Marie;Vingert, Benoit
红细胞输注的小鼠模型表明，与病毒或甲基化DNA相关的炎症促进红细胞同种免疫。在疫苗接种研究中，抗原特异性应答的强度取决于抗原和佐剂给药之间的延迟，短暂的延迟限制了免疫应答。在同种异体免疫小鼠模型中，注射Toll样受体激动剂和输血之间的延迟通常很短。在这项研究中，我们假设Toll样受体3激动剂给药的时间影响红细胞同种异体免疫。Poly（I：C）是一种Toll样受体3激动剂，在输注表达HEL的红细胞之前的不同时间点给予B10 BR小鼠。对于每个时间点，我们测量了脾HEL-presenting树突状细胞，HEL-specific CD 4（+）T细胞和血清中抗HEL抗体的活化。活化的免疫细胞的表型依赖于输血和Toll样受体依赖性炎症之间的延迟。在激动剂注射后7天输血时，抗HEL抗体的产生最高。在输血前3天注射poly（I：C）的小鼠中，产生白细胞介素-12的HEL-presenting CD 8 α（+）树突状细胞的比例最高。尽管两组之间早期诱导的HEL-specific CD 4（+）T细胞的数量相似，但在输血前7天注射poly（I：C）的小鼠中，这些细胞的高比例表达CD 134、CD 40和CD 44。这项研究清楚地表明，输血和Toll样受体诱导的炎症之间的延迟影响了对输注红细胞的免疫反应。
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 CD8 alpha(+) 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.