Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment.
Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment.
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DOI：
10.1111/j.1537-2995.2009.02333.x
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发表时间：
2009-12
期刊：
影响因子：
2.9
通讯作者：
Norris PJ
中科院分区：
文献类型：
--
作者：
Jackman RP;Heitman JW;Marschner S;Goodrich RP;Norris PJ
输血产品中存在的供体白色血细胞（WBC）可导致免疫后遗症，如在易感输血受者中产生抗HLA抗体或GVHD。消除血液制品的免疫原性可能被证明具有临床益处，特别是在需要多次输血的患者中，这些患者常见同种异体致敏。本研究探讨了一种基于核黄素存在下的紫外光照射减少病原体的方法。除了病原体之外，用该系统处理的WBC也受到影响，并且不能刺激体外同种异体PBMC的增殖。本研究试图确定调节这种免疫原性丧失的机制。检查经处理的细胞的参与活化和粘附、活力、细胞-细胞缀合的许多分子的表面表达，以及刺激同种异体PBMC中的免疫应答的能力。与未处理的对照组相比，UV照射的抗原呈递细胞显示HLA II类和共刺激分子的表面表达略有减少，并且许多粘附分子的表面表达有更显著的减少。此外，经处理的细胞在细胞-细胞接合中具有严重缺陷。观察到免疫原性几乎完全丧失，UV照射的细胞刺激几乎不可测量的IFN-γ产生，并且在同种异体特异性致敏的T细胞中没有可检测的STAT-3、STAT-5或CD 3-ε磷酸化。这些结果表明，有缺陷的细胞-细胞粘附阻止UV照射的细胞诱导T细胞活化。
Donor white blood cells (WBCs) present in transfusion products can lead to immune sequelae such as production of anti-HLA antibodies or GVHD in susceptible transfusion recipients. Eliminating the immunogenicity of blood products may prove to be of clinical benefit, particularly in patients requiring multiple transfusions in whom allosensitization is common. This study examines a method of pathogen reduction based on UV light illumination in the presence of riboflavin. In addition to pathogens, WBCs treated with this system are also affected and fail to stimulate proliferation of allogeneic PBMCs in vitro. This study sought to determine the mechanisms regulating this loss of immunogenicity. Treated cells were examined for surface expression of a number of molecules involved in activation and adhesion, viability, cell-cell conjugation, and ability to stimulate immune responses in allogeneic PBMCs. Compared with untreated controls, UV irradiated antigen presenting cells showed slightly reduced surface expression of HLA class II and costimulatory molecules and had more significant reductions in surface expression of a number of adhesion molecules. Furthermore, treated cells had a severe defect in cell-cell conjugation. The observed loss of immunogenicity was nearly complete, with UV irradiated cells stimulating barely measurable IFN-γ production and no detectable STAT-3, STAT-5, or CD3-ε phosphorylation in allospecific primed T cells. These results suggest that defective cell-cell adhesion prevents UV irradiated cells from inducing T cell activation.