Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood.
Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood.
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DOI：
10.1111/trf.13895
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发表时间：
2017-02
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;Muench MO;Inglis H;Heitman JW;Marschner S;Goodrich RP;Norris PJ
同种异体输血可导致针对主要组织相容性复合体（MHC）抗原的免疫应答，可能使未来的输血或移植复杂化。我们以前已经表明，病原体减少富含血小板的血浆（PRP）与核黄素和紫外线（UV+R）可以防止同种异体免疫小鼠。目前正在开发一种类似的病原体减少治疗方法，用于使用核黄素和更高剂量的紫外线治疗全血。我们试图确定这种治疗在预防同种免疫方面的有效性。BALB/c小鼠输注未经处理或经UV+R处理的同种异体C57 B1/6全血，伴或不伴白细胞减少。评价小鼠的供体特异性抗体和离体脾细胞细胞因子应答，以及调节性T（Treg）细胞频率的变化。UV+R处理阻断了细胞因子引发并降低了对输注全血的抗MHC同种抗体应答。白细胞减少降低了未处理组和UV+R组的同种抗体水平。当随后输注来自相同供体类型的未经处理的血液时，输注UV+R处理的全血的小鼠具有降低的同种抗体和细胞因子应答。这种反应的减少与Treg细胞的增加无关。用UV+R减少全血中的病原体显著减少，但不能消除同种免疫应答。暴露于UV+R处理的全血输注似乎诱导对同种异体抗原的耐受性，导致抗MHC同种异体抗体和细胞因子对随后暴露于相同同种异体抗原的反应降低。这种耐受性似乎不是由Treg细胞的增加驱动的。
Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We have previously shown that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and UV light (UV+R) can prevent alloimmunization in mice. A similar pathogen reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in prevention of alloimmunization. BALB/c mice were transfused with untreated or UV+R treated allogeneic C57Bl/6 whole blood with or without leukoreduction. Mice were evaluated for donor specific antibodies and ex vivo splenocyte cytokine responses, as well as for changes in the frequency of regulatory T (Treg) cells. UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R groups. Mice transfused with UV+R treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased Treg cells. Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate the alloimmune response. Exposure to UV+R treated whole blood transfusion does appear to induce tolerance to alloantigens resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in Treg cells.