Dendritic Cells Genetically Engineered to Express IL-10 Induce Long-Lasting Antigen-Specific Tolerance in Experimental Asthma
Dendritic Cells Genetically Engineered to Express IL-10 Induce Long-Lasting Antigen-Specific Tolerance in Experimental Asthma
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DOI：
10.4049/jimmunol.181.10.7230
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Bureau, Fabrice
中科院分区：
文献类型：
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作者：
Henry, Emmanuelle;Desmet, Christophe J.;Bureau, Fabrice
树突状细胞（Dendritic cells，DC）是一种专职的APC，具有启动包括致耐受性应答在内的初级免疫应答的独特能力。我们已经基因工程骨髓来源的DC表达免疫抑制细胞因子IL-10，并测试这些细胞控制实验性哮喘的能力。在OVA致敏和激发之前，向幼稚小鼠单次气管内注射OVA脉冲的IL-10转导的DC（OVA-IL-10-DC）防止了气道过敏的所有主要特征，即嗜酸性气道炎症、气道高反应性和粘液、Ag特异性Ig和IL-4的产生。OVA-IL-10-DCs还逆转了已建立的实验性哮喘，并具有持久和Ag特异性作用。通过使用IL-10缺陷小鼠，我们进一步显示宿主IL-10是介导OVA-IL-10-DC的免疫调节作用所必需的，并且证明了在OVA-IL-10-DC注射小鼠的纵隔淋巴结中，OVA特异性CD 4（+）CD 25（+）Foxp 3（+）IL-10（+）调节性T细胞的百分比显著增加。最后，过继转移来自注射OVA-IL-10-DCs小鼠的CD 4（+）纵隔淋巴结T细胞可保护OVA致敏的受者免受OVA激发后的气道嗜酸性粒细胞增多。我们的研究描述了一个有前途的策略，以诱导持久的银特异性气道过敏耐受。免疫学杂志，2008，181：7230-7242.
Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4(+)CD25(+)Foxp3(+)IL-10(+) regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4(+) mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy. The Journal of Immunology, 2008, 181: 7230-7242.