Lambrecht B N, Peleman R A, Bullock G R, Pauwels R A
Respiratory Diseases; Pathology, University Hospital Ghent, Belgium.
Clin Exp Allergy. 2000 Feb;30(2):214-24. doi: 10.1046/j.1365-2222.2000.00818.x.
Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo.
Rats were immunized by intratracheal instillation of ovalbumin (OVA) -pulsed bone marrow-derived DCs or macrophages and exposed 10 days later to a 30-min aerosol of OVA on 3 consecutive days. Total and differential cell counts and flow cytometry on bronchoalveolar lavage (BAL) fluid, airway histology and serum OVA-immunoglobulin (Ig) E levels were analysed 24 h after the last exposure.
As few as 2 x 104 OVA-DC induced sensitization to inhaled OVA. The secondary response to OVA-aerosol consisted of an antigen-specific increase in the number of bronchoalveolar mononuclear cells, activated CD4-positive alphabeta-TCR T lymphocytes, neutrophils and few eosinophils. Peribronchial and perivascular mononuclear cell infiltrates were seen on histological analysis. There was no production of systemic OVA-IgE. Bone marrow-derived macrophages did not induce sensitization.
Delivering antigen to the respiratory tract via professional antigen-presenting DCs sensitizes for a secondary response to inhaled antigen leading to airway inflammation. This model will prove very useful for studying the early events of sensitization to inhaled antigen using the respiratory route.
气道树突状细胞(DCs)捕获并呈递吸入的抗原。目前尚不清楚气道中DCs的抗原呈递是否足以在体内诱导对吸入抗原的致敏。
通过气管内滴注卵清蛋白(OVA)脉冲的骨髓来源的DCs或巨噬细胞对大鼠进行免疫,10天后连续3天让其暴露于30分钟的OVA气溶胶中。在最后一次暴露24小时后,分析支气管肺泡灌洗(BAL)液中的细胞总数和分类计数以及流式细胞术、气道组织学和血清OVA免疫球蛋白(Ig)E水平。
低至2×104个OVA-DC即可诱导对吸入OVA的致敏。对OVA气溶胶的二次反应包括支气管肺泡单核细胞、活化的CD4阳性αβ-TCR T淋巴细胞、中性粒细胞和少量嗜酸性粒细胞数量的抗原特异性增加。组织学分析可见支气管周围和血管周围单核细胞浸润。未产生全身性OVA-IgE。骨髓来源的巨噬细胞未诱导致敏。
通过专业的抗原呈递DCs将抗原递送至呼吸道可使机体对吸入抗原产生二次反应致敏,从而导致气道炎症。该模型对于利用呼吸道研究吸入抗原致敏的早期事件将非常有用。