Humphreys Ian R, Walzl Gerhard, Edwards Lorna, Rae Aaron, Hill Sue, Hussell Tracy
Imperial College of Science, Technology and Medicine, Exhibition Road, London SW7 2AZ, United Kingdom.
J Exp Med. 2003 Oct 20;198(8):1237-42. doi: 10.1084/jem.20030351.
Respiratory infections are the third leading cause of death worldwide. Illness is caused by pathogen replication and disruption of airway homeostasis by excessive expansion of cell numbers. One strategy to prevent lung immune-mediated damage involves reducing the cellular burden. To date, antiinflammatory strategies have affected both antigen-specific and naive immune repertoires. Here we report a novel form of immune intervention that specifically targets recently activated T cells alone. OX40 (CD134) is absent on naive T cells but up-regulated 1-2 d after antigen activation. OX40-immunoglobulin fusion proteins block the interaction of OX40 with its ligand on antigen-presenting cells and eliminate weight loss and cachexia without preventing virus clearance. Reduced proliferation and enhanced apoptosis of lung cells accompanied the improved clinical phenotype. Manipulation of this late costimulatory pathway has clear therapeutic potential for the treatment of dysregulated lung immune responses.
呼吸道感染是全球第三大致死原因。疾病是由病原体复制以及细胞数量过度增加破坏气道内环境稳态所致。预防肺部免疫介导损伤的一种策略是减轻细胞负担。迄今为止，抗炎策略已影响抗原特异性免疫库和天然免疫库。在此，我们报告一种新型免疫干预形式，该形式仅特异性靶向最近激活的T细胞。初始T细胞上不存在OX40（CD134），但在抗原激活后1 - 2天会上调。OX40免疫球蛋白融合蛋白可阻断OX40与其在抗原呈递细胞上的配体之间的相互作用，并消除体重减轻和恶病质，同时不影响病毒清除。肺部细胞增殖减少和凋亡增加伴随着临床表型的改善。操纵这种晚期共刺激途径在治疗失调的肺部免疫反应方面具有明确的治疗潜力。
