Graffi Sebastian J, Dekan Gerhard, Stingl Georg, Epstein Michelle M
Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, VIRCC, University of Vienna Medical School, A-1235, Austria.
Clin Immunol. 2002 May;103(2):176-84. doi: 10.1006/clim.2002.5190.
Antigen-pulsed dendritic cells (DCs) have been used extensively as cellular vaccines to induce a myriad of protective immune responses. Adoptive transfer of antigen-pulsed DCs is especially effective at generating Th1 and CD8 immune responses. However, recently this strategy has been shown to induce Th2 cells when DCs are administered locally into the respiratory tract. We sought to address whether systemic rather than local antigen-pulsed DC administration could induce Th2 experimental allergic asthma. We found that OVA-pulsed splenic DCs injected intraperitoneally induced polarized Th2 allergic lung disease upon secondary OVA aerosol challenge. Disease was characterized by eosinophilic lung inflammation, excess mucus production, airway hyperresponsiveness, and OVA-specific IgG1 and IgE. In addition, unusual pathology characterized by macrophage alveolitis and multinucleated giant cells was observed. These data show that systemic administration of antigen-pulsed DCs and subsequent aeroantigen challenge induces Th2 immunity. These findings have important implications for the development of DC-based vaccines.
抗原脉冲树突状细胞(DCs)已被广泛用作细胞疫苗,以诱导多种保护性免疫反应。抗原脉冲DCs的过继转移在产生Th1和CD8免疫反应方面特别有效。然而,最近有研究表明,当将DCs局部注入呼吸道时,这种策略会诱导Th2细胞。我们试图探讨全身而非局部给予抗原脉冲DCs是否会诱发Th2型实验性变应性哮喘。我们发现,腹腔注射卵清蛋白(OVA)脉冲的脾DCs,在再次进行OVA气雾剂激发后,会诱发极化的Th2型变应性肺部疾病。该疾病的特征为嗜酸性粒细胞性肺部炎症、黏液分泌过多、气道高反应性以及OVA特异性IgG1和IgE。此外,还观察到以巨噬细胞肺泡炎和多核巨细胞为特征的异常病理表现。这些数据表明,全身给予抗原脉冲DCs并随后进行气源性抗原激发可诱导Th2免疫。这些发现对基于DC的疫苗的开发具有重要意义。