Centre de Recherche en Transplantation et Immunologie (CRTI) UMR1064, INSERM, Université de Nantes, Nantes, 44093, France.
OSE Immunotherapeutics, Nantes, 44200, France.
Nat Commun. 2018 Oct 26;9(1):4483. doi: 10.1038/s41467-018-06804-y.
Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Here we investigate the therapeutic efficacy and mechanism of new anti-human IL-7Rα monoclonal antibodies (mAb) in non-human primates and show that, depending on the target epitope, a single injection of antagonistic anti-IL-7Rα mAbs induces a long-term control of skin inflammation despite repeated antigen challenges in presensitized monkeys. No modification in T cell numbers, phenotype, function or metabolism is observed in the peripheral blood or in response to polyclonal stimulation ex vivo. However, long-term in vivo hyporesponsiveness is associated with a significant decrease in the frequency of antigen-specific T cells producing IFN-γ upon antigen restimulation ex vivo. These findings indicate that chronic antigen-specific memory T cell responses can be controlled by anti-IL-7Rα mAbs, promoting and maintaining remission in T-cell mediated chronic inflammatory diseases.
针对致病性记忆免疫细胞的扩增是预防慢性自身免疫攻击的一种有前途的治疗策略。在这里，我们研究了新型抗人白细胞介素-7 受体 α 单克隆抗体（mAb）在非人类灵长类动物中的治疗效果和机制，并表明，根据靶表位的不同，单次注射拮抗抗白细胞介素-7 受体 α mAb 可在预先致敏的猴子中反复抗原挑战的情况下，长期控制皮肤炎症。在外周血或体外对多克隆刺激的反应中，未观察到 T 细胞数量、表型、功能或代谢的改变。然而，体内长期低反应性与抗原特异性 T 细胞产生 IFN-γ的频率在体外抗原再刺激时显著降低有关。这些发现表明，抗白细胞介素-7 受体 α mAb 可控制慢性抗原特异性记忆 T 细胞反应，促进和维持 T 细胞介导的慢性炎症性疾病的缓解。
