Bridging channel dendritic cells induce immunity to transfused red blood cells.
Bridging channel dendritic cells induce immunity to transfused red blood cells.
复制标题
桥接通道树突状细胞可诱导对输血的红细胞的免疫力。
DOI：
10.1084/jem.20151720
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发表时间：
2016-05-30
期刊：
影响因子：
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通讯作者：
Eisenbarth SC
中科院分区：
文献类型：
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作者：
Calabro S;Gallman A;Gowthaman U;Liu D;Chen P;Liu J;Krishnaswamy JK;Nascimento MS;Xu L;Patel SR;Williams A;Tormey CA;Hod EA;Spitalnik SL;Zimring JC;Hendrickson JE;Stowell SR;Eisenbarth SC
卡拉布罗等人。表明存在于脾桥通道中的 33D1+ 树突状细胞对于同种抗体对输注红细胞的反应至关重要。红细胞（RBC）输注是一种挽救生命的治疗工具。然而，输血受者的一个主要并发症是在供体红细胞上产生针对非 ABO 同种异体抗原的抗体，可能导致溶血和肾衰竭。长效抗体反应通常需要 CD4+ T 细胞的帮助，并且在小鼠输血模型中，同种免疫需要脾脏。然而，尚不清楚红细胞衍生的抗原如何呈递给脾脏中的幼稚 T 细胞。我们试图回答脾树突状细胞 (DC) 是否对于 T 细胞引发红细胞同种异体抗原至关重要。即使输注的红细胞在循环中持续存在数周，输注时常规 DC 的瞬时缺失或红细胞输注前脾脏 DC 的预激活也会消除 T 细胞和 B 细胞对同种异体红细胞的反应。尽管所有脾DC在体外均吞噬RBC并激活RBC特异性CD4+T细胞，但体内同种免疫仅需要桥接通道33D1+DC。相比之下，XCR1+CD8+ DC 的缺失并没有改变对红细胞的免疫反应。我们的工作表明，在红细胞输注期间的狭窄时间窗口内阻断一个 DC 子集的功能可能会预防需要终生红细胞输血支持的患者中发生的有害免疫反应。
Calabro et al. show that 33D1+ dendritic cells present in the bridging channel of the spleen are essential for alloantibody response to transfused red blood cells. Red blood cell (RBC) transfusion is a life-saving therapeutic tool. However, a major complication in transfusion recipients is the generation of antibodies against non-ABO alloantigens on donor RBCs, potentially resulting in hemolysis and renal failure. Long-lived antibody responses typically require CD4+ T cell help and, in murine transfusion models, alloimmunization requires a spleen. Yet, it is not known how RBC-derived antigens are presented to naive T cells in the spleen. We sought to answer whether splenic dendritic cells (DCs) were essential for T cell priming to RBC alloantigens. Transient deletion of conventional DCs at the time of transfusion or splenic DC preactivation before RBC transfusion abrogated T and B cell responses to allogeneic RBCs, even though transfused RBCs persisted in the circulation for weeks. Although all splenic DCs phagocytosed RBCs and activated RBC-specific CD4+ T cells in vitro, only bridging channel 33D1+ DCs were required for alloimmunization in vivo. In contrast, deletion of XCR1+CD8+ DCs did not alter the immune response to RBCs. Our work suggests that blocking the function of one DC subset during a narrow window of time during RBC transfusion could potentially prevent the detrimental immune response that occurs in patients who require lifelong RBC transfusion support.