Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells
Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells
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DOI：
10.1182/blood-2007-03-083105
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发表时间：
2007-10-01
期刊：
影响因子：
20.3
通讯作者：
Zimring, James C.
中科院分区：
文献类型：
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作者：
Hendrickson, Jeanne E.;Chadwick, Traci E.;Zimring, James C.
调节患者对红细胞（RBC）抗原产生同种免疫的因素知之甚少。使用小鼠输血模型，我们最近报道，病毒样炎症与聚肌胞苷酸[聚（I：C）]显着增强红细胞同种异体免疫。在此，我们测试的假设，聚（I：C）发挥这种作用，至少部分，在抗原呈递细胞（APC）的水平。使用一种新的体内方法，我们报告说，在非炎症状态下，大多数输注的红细胞被脾巨噬细胞消耗，只有微量消耗脾树突状细胞（DC）。在较小程度上，RBC也被肝脏中的APC消耗。然而，与可溶性抗原不同，淋巴结中的APC不消耗RBC。炎症与聚（I：C）诱导显着的消耗输注的红细胞脾树突状细胞，伴随着共刺激分子的表达增加。此外，这导致mHEL RBC同种异体抗原特异性的CD4（+）T细胞增殖增加。最后，脾切除取消了poly（I：C）对RBC同种免疫的增强作用。总之，这些数据提供了对输注RBC作为免疫原的性质的额外了解，并提供了病毒样炎症增强输注RBC的同种免疫的机制。
Factors regulating which patients become alloimmunized to red blood cell (RBC) antigens are poorly understood. Using a murine model of transfusion, we recently reported that viral-like inflammation with polyinosinic polycytidylic acid [poly (I:C)] significantly enhances RBC alloimmunization. Herein, we tested the hypothesis that poly (I:C) exerts this effect, at least in part, at the level of antigen-presenting cells (APCs). Using a novel in vivo method, we report that in the noninflamed state, most transfused RBCs were consumed by splenic macrophages, with only trace consumption by splenic dendritic cells (DCs). To a lesser extent, RBCs were also consumed by APCs in the liver. However, unlike soluble antigens, no RBCs were consumed by APCs in the lymph nodes. Inflammation with poly (I:C) induced significant consumption of transfused RBCs by splenic DCs, with a concomitant increase in costimulatory molecule expression. Moreover, this resulted in increased proliferation of CD4(+) T cells specific for the mHEL RBC alloantigen. Finally, splenectomy abrogated the enhancing effects of poly (I:C) on RBC alloimmunization. Together, these data provide additional insight into the nature of transfused RBCs as an immunogen and provide a mechanism by which viral-like inflammation enhances alloimmunization to transfused RBCs.