Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion
Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion
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DOI：
10.4049/jimmunol.1601736
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Stowell, Sean R.
中科院分区：
文献类型：
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作者：
Arthur, Connie M.;Patel, Seema R.;Stowell, Sean R.
尽管红细胞输注可导致抗红细胞同种异体抗体的产生，从而增加危及生命的溶血性输血反应的概率，但并不是所有的患者都会产生抗红细胞同种异体抗体。然而，调节红细胞输注免疫反应的因素仍不完全清楚。可能影响同种异体抗体形成的一个变量是RBC同种异体抗原密度。RBC同种异体抗原在RBC表面以不同的密度存在，同样显示出不同的诱导RBC同种抗体形成的倾向。然而，尽管不同的同种异体抗原以不同的水平存在于红细胞表面，但大多数同种异体抗原也表现出完全不同的结构，这使得很难将银密度差异的潜在影响与其他可能影响红细胞同种异体免疫的同种异体抗原特征分开。为了解决这个问题，我们产生了在不同水平上稳定表达相同Ag的红细胞。尽管暴露于高抗原水平的红细胞可诱导出较强的抗体反应，但低抗原水平的红细胞不能诱导RBC同种异体抗体。然而，暴露在低银密度的红细胞中并不是没有后果，因为受者随后会产生银特异性耐受性。低银密度红细胞诱导的耐受保护高银密度红细胞免受免疫介导的清除，是抗原特异性的，并通过诱导B细胞无反应性发生。这些结果表明，Ag浓度可以有效地影响RBC输注后的免疫结果，并提示Ag水平改变的红细胞可能提供了一种独特的工具来诱导Ag特异性耐受。
Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinct propensities to induce RBC alloantibody formation. However, although distinct alloantigens reside on the RBC surface at different levels, most alloantigens also represent completely different structures, making it difficult to separate the potential impact of differences in Ag density from other alloantigen features that may also influence RBC alloimmunization. To address this, we generated RBCs that stably express the same Ag at different levels. Although exposure to RBCs with higher Ag levels induces a robust Ab response, RBCs bearing low Ag levels fail to induce RBC alloantibodies. However, exposure to low Ag-density RBCs is not without consequence, because recipients subsequently develop Ag-specific tolerance. Low Ag-density RBC-induced tolerance protects higher Ag-density RBCs from immune-mediated clearance, is Ag specific, and occurs through the induction of B cell unresponsiveness. These results demonstrate that Ag density can potently impact immune outcomes following RBC transfusion and suggest that RBCs with altered Ag levels may provide a unique tool to induce Ag-specific tolerance.