Wells J W, Choy K, Lloyd C M, Noble A
King's College London, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Guy's Hospital, London, UK.
Mucosal Immunol. 2009 Jan;2(1):54-62. doi: 10.1038/mi.2008.69. Epub 2008 Oct 29.
CD8 T cells are known to deviate CD4 T-cell responses from Th2 toward Th1. Reduction of Th2 cytokines and increased interferon-gamma ameliorates allergic airway disease. We have developed a novel approach to the suppression of allergic airway inflammation, by designing a MHC class I-restricted allergen peptide vaccine, which induces potent and long-lived CD8 T-cell responses. Vaccination of C57BL/6 mice before allergen sensitization completely prevented allergen-specific immunoglobulin E (IgE) antibody responses. Vaccination after sensitization failed to suppress IgE, but inhibited accumulation of eosinophils and neutrophils in airways after subsequent allergen challenge. Vaccination suppressed Th2 airway infiltration and enhanced the lung Th1 response without inducing excessive CD8 cellular infiltration or interleukin-17, and the combination of class I peptide with adjuvant was more effective than adjuvant alone. Airway hyperreactivity was prevented by vaccination in an allergen-specific fashion. Class I peptide vaccines might therefore represent a robust and long-lasting immunotherapeutic strategy in allergic disease.
已知CD8 T细胞会使CD4 T细胞反应从Th2型偏向Th1型。Th2细胞因子减少以及干扰素-γ增加可改善过敏性气道疾病。我们通过设计一种I类主要组织相容性复合体(MHC)限制性变应原肽疫苗,开发出了一种抑制过敏性气道炎症的新方法,该疫苗可诱导强效且持久的CD8 T细胞反应。在变应原致敏前对C57BL/6小鼠进行疫苗接种可完全预防变应原特异性免疫球蛋白E(IgE)抗体反应。致敏后接种疫苗未能抑制IgE,但在随后的变应原激发后可抑制气道中嗜酸性粒细胞和中性粒细胞的聚集。接种疫苗可抑制Th2细胞向气道浸润,并增强肺部Th1反应,且不会诱导过度的CD8细胞浸润或白细胞介素-17,I类肽与佐剂联合使用比单独使用佐剂更有效。接种疫苗以变应原特异性方式预防了气道高反应性。因此,I类肽疫苗可能代表了一种用于过敏性疾病的强大且持久的免疫治疗策略。