Swiss Institute for Allergy and Asthma Research (SIAF), Davos, Switzerland; Department and Clinic of Internal Diseases, Geriatry and Allergology, Wroclaw Medical University, Wroclaw, Poland.
Allergy. 2014 Sep;69(9):1162-70. doi: 10.1111/all.12461. Epub 2014 Jul 12.
Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses.
In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules.
MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1β, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2.
This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.
变应原特异性免疫疗法（SIT）面临着与副作用和疗效有限相关的问题。直接将变应原提取物注入淋巴结会诱导更高的特异性 IgG 产生和 T 细胞反应，同时使用的变应原剂量更低。
在这项研究中，我们研究了 MAT 疫苗在体外和猫过敏鼻炎患者过敏原 SIT 中的免疫调节机制，这些患者接受了 3 次腹股沟淋巴结内 MAT-Fel d 1 疫苗注射，我们在 PBMC 和细胞培养物中研究了特定 T 细胞增殖、Fel d 1-四聚体特异性反应以及多种免疫调节分子。
MAT-Fel d 1 疫苗被抗原呈递细胞有效内化。随后前半胱天冬酶 1 被切割为半胱天冬酶 1，并且分泌了白细胞介素 1β，表明炎症小体的激活。Mat-Fel d 1 在比 Fel d 1 低 100 倍的剂量下诱导了特定的 T 细胞增殖和以白细胞介素 10 和干扰素-γ为主的 T 细胞反应，同时降低了 Th2 细胞因子。MAT-Fel d 1-ILIT 通过多种免疫抑制机制诱导免疫耐受。在 MAT-Fel d 1 组中，在 1 年后，早期 Fel d 1 特异性 T 细胞激活后，T 细胞对变应原完全无反应，其特征为增加了变应原特异性调节性 T 细胞、循环中 Fel d 1 四聚体阳性细胞减少、白细胞介素 10 和 FOXP3 表达增加以及 HR2/HR1 比值向 HR2 方向改变。
这项研究表明，通过增加变应原的细胞内化、炎症小体的激活和产生变应原特异性外周 T 细胞耐受，3 次淋巴结内注射 MAT-Fel d 1 疫苗可诱导变应原耐受。
