Immune modulation and lack of alloimmunization following transfusion with pathogen-reduced platelets in mice
Immune modulation and lack of alloimmunization following transfusion with pathogen-reduced platelets in mice
复制标题
DOI：
10.1111/trf.12133
复制
发表时间：
2013-11-01
期刊：
影响因子：
2.9
通讯作者：
Norris, Philip J.
中科院分区：
文献类型：
--
作者：
Jackman, Rachael P.;Muench, Marcus O.;Norris, Philip J.
背景同种异体血液制品的输注可导致同种异体免疫，影响后续输血和实体器官移植的成功。使用核黄素和紫外线B（UVB）光的病原体减少已经显示通过下调表面粘附分子、有效地阻断细胞-细胞接合和直接呈递来消除体外白色血细胞（WBC）的免疫原性。我们试图确定这种免疫原性的损失是否在体内延长，其中间接介绍同种异体antigens can occur.Study Design and MethodsBALB/cJ小鼠输注未经处理或核黄素和UVB处理的C57 B1/6 J富含血小板的血浆（PRP）含有白细胞。测量循环同种抗体和同种特异性脾细胞细胞因子反应。结果输血前使用核黄素和UVB光减少同种异基因WBC富集的PRP的病原体，阻止了同种免疫，同时失去了同种抗体的产生和离体二级细胞因子反应的启动。当给予处理输血的小鼠随后给予未处理的输血时，它们产生正常水平的同种抗体，但离体二级细胞因子反应降低。这种免疫调节是抗原特异性的，并依赖于白细胞在处理product.ConclusionsUVB加核黄素治疗的白细胞富集PRP有效地阻断同种免疫，并调节免疫反应，随后的曝光。
BackgroundTransfusion of allogeneic blood products can lead to alloimmunization, impacting success of subsequent transfusions and solid organ transplants. Pathogen reduction using riboflavin and ultravioletB (UVB) light has been shown to eliminate the immunogenicity of white blood cells (WBCs) in vitro through down regulation of surface adhesion molecules, effectively blocking cell-cell conjugation and direct presentation. We sought to determine if this loss of immunogenicity is extended in vivo where indirect presentation of allogeneic antigens can occur.Study Design and MethodsBALB/cJ mice were transfused with either untreated or riboflavin and UVB-treated C57Bl/6J platelet-rich plasma (PRP) containing WBCs. Circulating alloantibody and allospecific splenocyte cytokine responses were measured.ResultsPathogen reduction of allogeneic WBC-enriched PRP using riboflavin and UVB light before transfusion prevented alloimmunization, with a loss of both alloantibody generation and priming of secondary cytokine responses ex vivo. When mice given treated transfusions were subsequently given untreated transfusions, they produced normal levels of alloantibodies but had reduced secondary cytokine responses ex vivo. This immune modulation was antigen specific and was dependent on the presence of WBCs in the treated product.ConclusionsUVB plus riboflavin treatment of WBC-enriched PRP effectively blocks alloimmunization and modulates immune responses to subsequent exposures.