The spleen plays a central role in primary humoral alloimmunization to transfused mHEL red blood cells.
The spleen plays a central role in primary humoral alloimmunization to transfused mHEL red blood cells.
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DOI：
10.1111/j.1537-2995.2009.02200.x
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发表时间：
2009-08
期刊：
影响因子：
2.9
通讯作者：
Zimring JC
中科院分区：
文献类型：
--
作者：
Hendrickson JE;Saakadze N;Cadwell CM;Upton JW;Mocarski ES;Hillyer CD;Zimring JC
输注的红细胞 (RBC) 上的抗原与其他免疫原之间存在一些差异，包括解剖学区隔。来自微生物病原体和实体器官移植物的抗原会流入局部淋巴结，而循环红细胞则在外周循环中保持隔离，并被脾脏和肝脏中的抗原呈递细胞 (APC) 消耗。因此，推测脾脏 APC 在输注红细胞的初次同种免疫中发挥核心作用。受体小鼠被切除脾脏并输注表达膜结合鸡蛋溶菌酶（mHEL）模型红细胞抗原的转基因红细胞。在一些实验中，mHEL 特异性 CD4+ T 细胞被过继转移到受体小鼠中，以研究辅助 T 细胞反应。未操作或假脾切除的小鼠作为对照。表达 mHEL 的重组鼠巨细胞病毒 (mHEL-MCMV) 用作对照非红细胞免疫原。通过 mHEL 特异性酶联免疫吸附测定和基于流式细胞仪的红细胞交叉配血来测量体液反应。对照动物在单次 mHEL RBC 输注后合成了可检测的抗 HEL 免疫球蛋白 (Ig)G。 mHEL 特异性 CD4+ T 细胞经历了强劲的扩增，CD4+ T 细胞的过继转移导致抗 HEL IgG 增加了 1000 倍。相比之下，在脾切除小鼠中可检测到最低限度的抗 HEL IgG，mHEL 特异性 CD4+ T 细胞不会增殖，并且过继转移不会增加抗 HEL IgG。然而，暴露于 mHEL-MCMV 后，对照小鼠和脾切除小鼠的抗 HEL IgG 反应是相同的。总之，这些发现说明了输注红细胞作为免疫刺激的独特特性，其中脾脏在 CD4+ T 细胞激活水平上的初级红细胞同种免疫中发挥着关键作用。
Several differences exist between antigens on transfused red blood cells (RBCs) and other immunogens, including anatomical compartmentalization. Whereas antigens from microbial pathogens and solid organ transplants drain into local lymph nodes, circulating RBCs remain segregated in the peripheral circulation, where they are consumed by antigen-presenting cells (APCs) in the spleen and liver. Accordingly, it was hypothesized that the splenic APCs play a central role in primary alloimmunization to transfused RBCs. Recipient mice were splenectomized and transfused with transgenic RBCs expressing the membrane-bound hen egg lysozyme (mHEL) model RBC antigen. In some experiments, mHEL-specific CD4+ T cells were adoptively transferred into recipient mice to allow investigation of helper T-cell responses. Unmanipulated or sham-splenectomized mice served as controls. Recombinant murine cytomegalovirus expressing mHEL (mHEL-MCMV) was used as a control non-RBC immunogen. Humoral responses were measured by mHEL-specific enzyme-linked immunosorbent assay and flow cytometric–based RBC cross-match. Control animals synthesized detectable anti-HEL immunoglobulin (Ig)G after a single mHEL RBC transfusion. mHEL-specific CD4+ T cells underwent robust expansion, and adoptive transfer of CD4+ T cells resulted in a 1000-fold increase in anti-HEL IgG. In contrast, minimal anti-HEL IgG was detectable in splenectomized mice, mHEL-specific CD4+ T cells did not proliferate, and adoptive transfer did not increase anti-HEL IgG. However, anti-HEL IgG response after exposure to mHEL-MCMV was equivalent in control and splenectomized mice. Together, these findings illustrate the distinct properties of transfused RBCs as immunologic stimuli, with the spleen playing a critical role in primary RBC alloimmunization at the level of CD4+ T-cell activation.