Yale University School of Medicine, Department of Pediatrics, New Haven, CT, Unites States of America.
Yale University School of Medicine, Department of Laboratory Medicine, New Haven, CT, Unites States of America.
Blood Transfus. 2019 Sep;17(5):368-377. doi: 10.2450/2018.0178-18. Epub 2018 Nov 7.
Factors influencing the development of alloantibodies against blood group antigens on transfused red blood cells are poorly defined. We hypothesised that transfused platelets may act as a danger signal to recipients and affect humoral immune responses to transfused red blood cells.
Platelet-rich plasma prepared from wild-type C57BL/6 or CD40L knock-out donors was transfused into wild-type or CD40L knock-out recipients. Leucoreduced red blood cells from transgenic donors expressing high levels of the human KEL glycoprotein in an erythrocyte-specific manner (KEL donors) were transfused after the platelets, and anti-KEL responses were measured longitudinally. In some experiments, recipients were treated with poly (I:C), monoclonal CD40L-blocking antibody, or CD4-depleting antibody prior to transfusion.
Transfusion of wild-type C57BL/6 platelets or treatment with poly (I:C) prior to KEL red blood cell transfusion led to an anti-KEL alloimmune response in wild-type recipients. Transfusion of platelets from wild-type but not CD40L knock-out donors prior to KEL red blood cell transfusion led to an IgG anti-KEL alloimmune response in CD40L knock-out recipients; unexpectedly, transfusion of platelets from CD40L knock-out donors prior to KEL red blood cell transfusion led to a robust anti-KEL alloimmune response in wild-type recipients. Recipient treatment with MR1 CD40L-blocking antibody or CD4-depleting antibody prevented KEL alloimmunisation altogether.
Transfused platelets serve as an adjuvant in this T-dependent murine model of anti-KEL red blood cell alloimmunisation, with CD40/CD40L interactions being involved to some degree but with additional mechanisms also playing a role. These findings raise questions about the role that transfused or endogenous platelets may play in other innate/adaptive immune responses.
影响输注的红细胞上血型抗原同种抗体产生的因素尚未完全明确。我们假设输注的血小板可能作为一种危险信号，作用于受者，并影响对输注的红细胞的体液免疫反应。
从野生型 C57BL/6 或 CD40L 敲除供体中制备富含血小板的血浆，并输注给野生型或 CD40L 敲除受者。在输注血小板之后，输注来自以红细胞特异性方式表达高水平人 KEL 糖蛋白的转基因供体的白细胞减少的红细胞（KEL 供体），并进行纵向抗-KEL 反应的测量。在一些实验中，受者在输注前用多聚 I:C、单克隆 CD40L 阻断抗体或 CD4 耗竭抗体进行处理。
在 KEL 红细胞输注前输注野生型 C57BL/6 血小板或用多聚 I:C 处理，导致野生型受者产生抗-KEL 同种异体免疫反应。在 KEL 红细胞输注前输注来自野生型而非 CD40L 敲除供体的血小板，导致 CD40L 敲除受者产生 IgG 抗-KEL 同种异体免疫反应；出乎意料的是，在 KEL 红细胞输注前输注 CD40L 敲除供体的血小板，导致野生型受者产生强烈的抗-KEL 同种异体免疫反应。受者用 MR1 CD40L 阻断抗体或 CD4 耗竭抗体处理可完全阻止 KEL 同种免疫。
在这个依赖 T 细胞的抗-KEL 红细胞同种异体免疫的小鼠模型中，输注的血小板起佐剂作用，CD40/CD40L 相互作用在某种程度上涉及，但也存在其他机制发挥作用。这些发现引发了关于输注或内源性血小板在其他固有/适应性免疫反应中可能发挥的作用的问题。
