Vitalant Research Institute, San Francisco, CA, United States.
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States.
Front Immunol. 2023 Dec 11;14:1281130. doi: 10.3389/fimmu.2023.1281130. eCollection 2023.
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.
针对血小板抗原的同种免疫反应主要针对主要组织相容性复合体（MHC），可导致随后的血小板输注不良反应、血小板输注无效或未来移植排斥。血小板输注受者包括经历严重细菌或病毒感染的个体，其潜在健康状况如何调节血小板同种免疫尚未完全清楚。
本研究通过用聚肌苷酸-聚胞苷酸（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，研究潜在炎症对血小板同种免疫的影响，假设潜在炎症增强同种免疫。用 poly（I：C）、LPS 或无处理物预处理小鼠，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 MHC 特异性 B 细胞（allo-B 细胞）反应。使用 MHC 四聚体鉴定稀有同种 B 细胞群体。
与单独血小板输注相比，先前暴露于 poly（I：C）增加了对异体血小板输注的同种抗体反应，而先前暴露于 LPS 则降低了反应。与单独血小板输注相比，先前暴露于 poly（I：C）的 allo-B 细胞反应相等（如果不是适度降低），并且表现出更强的 allo-B 细胞记忆发育。相反，先前暴露于 LPS 导致 allo-B 细胞频率、激活、抗原经验和生发中心形成降低，并改变了记忆 B 细胞反应。
总之，并非所有炎症环境都增强旁观者反应，革兰氏阴性细菌的 LPS 介导的先前炎症实际上可能会抑制血小板同种免疫。
