Clinical Immunology and Allergy Division, University of São Paulo School of Medicine, São Paulo, Brazil.
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2021 Apr 22;12:655958. doi: 10.3389/fimmu.2021.655958. eCollection 2021.
Programmed cell death ligand 1(PDL-1) is known for its inhibitory effect on the cellular immune response. Even though it is expressed on the surface of mast cells, its role in allergic diseases is unknown. We analyzed the effects of PD-L1 blockade in a murine model of active cutaneous anaphylaxis (ACA). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Blood samples were collected to measure specific immunoglobulins. The mice were divided into six groups that underwent the active cutaneous anaphylaxis procedure. Group 1 (negative control) received 50 μl of phosphate-buffered saline (PBS) subcutaneously, and the other five groups were sensitized with 50 μg of OVA subcutaneously. Group 2 was the positive control, and the others received the anti-PD-L1 antibody or its isotype during sensitization (groups 3 and 4) or during the challenge (groups 5 and 6). All animals that underwent ACA on the ears with OVA and PBS were sacrificed, and the reaction was evaluated by extravasation of Evans blue (measured by spectrophotometry) and histological analysis of the collected fragments. Anti-PD-L1 blockade during the sensitization phase led to a reduction in specific IgE and IgG1 levels, allergic reaction intensity at the ACA site, and mast cell degranulation in the tissue. There was no significant biological effect of anti-PD-L1 administration on the challenge phase. PD-L1 blockade during allergen sensitization inhibited the synthesis of specific IgE and IgG1 and decreased mast cell activation in this murine model of anaphylaxis.
程序性死亡配体 1（PDL-1）以其对细胞免疫反应的抑制作用而闻名。尽管它在肥大细胞表面表达，但它在过敏疾病中的作用尚不清楚。我们分析了 PD-L1 阻断在活性皮肤过敏症（ACA）的小鼠模型中的作用。C57BL/6 小鼠用卵清蛋白（OVA）致敏和挑战。采集血样以测量特异性免疫球蛋白。将小鼠分为六组，进行活性皮肤过敏症程序。第 1 组（阴性对照）接受 50μl 磷酸盐缓冲盐水（PBS）皮下注射，其余五组用 50μg OVA 皮下致敏。第 2 组为阳性对照，其余组在致敏期间（第 3 和第 4 组）或在挑战期间（第 5 和第 6 组）接受抗 PD-L1 抗体或其同型。所有用 OVA 和 PBS 在耳朵上进行 ACA 的动物均被处死，并通过 Evans 蓝外渗（分光光度法测量）和收集的组织片段的组织学分析评估反应。在致敏阶段阻断 PD-L1 导致特异性 IgE 和 IgG1 水平降低、ACA 部位过敏反应强度降低以及组织中的肥大细胞脱颗粒。抗 PD-L1 给药对挑战阶段没有显著的生物学作用。在这种过敏症的小鼠模型中，在过敏原致敏期间阻断 PD-L1 抑制了特异性 IgE 和 IgG1 的合成，并减少了肥大细胞的激活。
