Enhanced alloresponse to platelet transfusion due to immune dysregulation following ablative chemotherapy in mice.
Enhanced alloresponse to platelet transfusion due to immune dysregulation following ablative chemotherapy in mice.
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DOI：
10.3389/fimmu.2023.1281123
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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同种免疫在血小板输注后很常见，可能会给受者带来负面结果，例如对随后的输血无效和移植排斥。健康人不接受输血，导致需要输血的疾病和治疗会对引入这些同种异体抗原的免疫环境产生重大影响。消融化疗在血小板接受者中很常见，并且具有有效的免疫学作用。在这项研究中，我们模拟了化疗对血小板输注同种异体反应的影响。由于化疗通常被认为具有免疫抑制作用，我们假设它们会导致同种异体反应减弱。 小鼠接受阿糖胞苷和阿霉素联合化疗治疗，然后输注同种异体血小板，并与未接受治疗、单独化疗或单独输血的对照组进行比较。输血后两周测量同种抗体反应，并随时间监测细胞反应和生长因子。与我们的假设相反，我们发现化疗导致对同种异体血小板输注的同种抗体反应增加。这种增强的反应是抗原特异性的，并且与 CD4+ 和 CD8+ T 细胞反应的增加有关。化疗导致淋巴细胞快速耗竭，随后进行重建、过渡性 B 细胞的非特异性激活（在最不成熟的亚群中激活水平最高）以及 B 细胞激活因子 (BAFF) 的血清水平升高。 这些数据表明，消融化疗会增加同种免疫的风险，如果临床得到证实，可能需要采取额外措施来保护这些患者群体。
Alloimmunization is common following platelet transfusion and can result in negative outcomes for recipients such as refractoriness to subsequent transfusions and rejection of transplants. Healthy people do not receive blood transfusions, and the diseases and therapies that result in a need to transfuse have significant impacts on the immunological environment to which these alloantigens are introduced. Ablative chemotherapies are common among platelet recipients and have potent immunological effects. In this study, we modeled the impact of chemotherapy on the alloresponse to platelet transfusion. As chemotherapies are generally regarded as immunosuppressive, we hypothesized that that they would result in a diminished alloresponse. Mice were given a combination chemotherapeutic treatment of cytarabine and doxorubicin followed by transfusion of allogeneic platelets, and compared to controls given no treatment, chemotherapy alone, or transfusion alone. Alloantibody responses were measured 2 weeks after transfusion, and cellular responses and growth factors were monitored over time. Contrary to our hypothesis, we found that chemotherapy led to increased alloantibody responses to allogeneic platelet transfusion. This enhanced response was antigen-specific and was associated with increased CD4+ and CD8+ T cell responses. Chemotherapy led to rapid lymphocyte depletion followed by reconstitution, non-specific activation of transitional B cells with the highest levels of activation in the least mature subsets, and increased serum levels of B cell activating factor (BAFF). These data suggest that ablative chemotherapy can increase the risk of alloimmunization and, if confirmed clinically, that additional measures to protect these patient populations may be warranted.
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影响因子：
2.9
作者：
Jackman, Rachael P.;Muench, Marcus O.;Norris, Philip J.
通讯作者：
Norris, Philip J.
影响因子：
2.7
作者：
Hess, J. R.;Trachtenberg, F. L.;Slichter, S. J.
通讯作者：
Slichter, S. J.
尖端：BAFF通过过渡B细胞的TACI依赖性激活促进自身抗体的产生。
DOI：
10.4049/jimmunol.1600017
发表时间：
2016-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacobs HM;Thouvenel CD;Leach S;Arkatkar T;Metzler G;Scharping NE;Kolhatkar NS;Rawlings DJ;Jackson SW
通讯作者：
Jackson SW
影响因子：
37.8
作者：
Itescu, S;Tung, TC;Michler, RE
通讯作者：
Michler, RE
DOI：
10.6004/jnccn.2015.0151
发表时间：
2015-10-01
影响因子：
13.4
作者：
Grossman, Stuart A.;Ellsworth, Susannah;Ye, Xiaobu
通讯作者：
Ye, Xiaobu