Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice.

Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice.
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DOI:
10.3389/fimmu.2023.1281130
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发表时间:
2023
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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针对主要靶向主要组织相容性复合体(MHC)的血小板抗原的同种免疫应答可引起随后的血小板输注的不良反应、血小板难治性或未来移植的排斥。血小板输注接受者包括经历严重细菌或病毒感染的个体,并且他们的潜在健康如何调节血小板同种异体免疫尚不清楚。本研究通过用聚肌胞苷酸(poly(I:C))模拟病毒样炎症或用脂多糖(LPS)模拟革兰氏阴性细菌感染,研究了潜在炎症对血小板同种异体免疫的影响,假设潜在炎症增强同种异体免疫。小鼠用poly(I:C)、LPS或无预处理,然后输注非白细胞减少或白细胞减少的血小板。两周后评估同种抗体和同种异体MHC特异性B细胞(allo-B细胞)应答。使用MHC四聚体鉴定了罕见的同种异体B细胞群体。相对于单独的血小板输注,先前暴露于poly(I:C)增加了对同种异体血小板输注的同种抗体反应,而先前暴露于LPS减少了反应。既往暴露于poly(I:C)的allo-B细胞应答与单独输注血小板的allo-B细胞应答相当(如果不是中度降低),并且表现出更稳健的allo-B细胞记忆发育。相反,先前暴露于LPS导致减少的allo-B细胞频率、活化、抗原经历和生发中心形成以及改变的记忆B细胞应答。 总之,并不是所有的炎症环境都能增强旁观者反应,并且革兰氏阴性菌上LPS介导的先前炎症实际上可能会减少血小板同种异体免疫。
Alloimmune responses against platelet antigens, which dominantly target the major histocompatibility complex (MHC), can cause adverse reactions to subsequent platelet transfusions, platelet refractoriness, or rejection of future transplants. Platelet transfusion recipients include individuals experiencing severe bacterial or viral infections, and how their underlying health modulates platelet alloimmunity is not well understood. This study investigated the effect of underlying inflammation on platelet alloimmunization by modelling viral-like inflammation with polyinosinic-polycytidylic acid (poly(I:C)) or gram-negative bacterial infection with lipopolysaccharide (LPS), hypothesizing that underlying inflammation enhances alloimmunization. Mice were pretreated with poly(I:C), LPS, or nothing, then transfused with non-leukoreduced or leukoreduced platelets. Alloantibodies and allogeneic MHC-specific B cell (allo-B cell) responses were evaluated two weeks later. Rare populations of allo-B cells were identified using MHC tetramers. Relative to platelet transfusion alone, prior exposure to poly(I:C) increased the alloantibody response to allogeneic platelet transfusion whereas prior exposure to LPS diminished responses. Prior exposure to poly(I:C) had equivalent, if not moderately diminished, allo-B cell responses relative to platelet transfusion alone and exhibited more robust allo-B cell memory development. Conversely, prior exposure to LPS resulted in diminished allo-B cell frequency, activation, antigen experience, and germinal center formation and altered memory B cell responses. In conclusion, not all inflammatory environments enhance bystander responses and prior inflammation mediated by LPS on gram-negative bacteria may in fact curtail platelet alloimmunization.
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