Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity
Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity
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DOI：
10.4049/jimmunol.172.6.3612
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Fujihashi, K
中科院分区：
文献类型：
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作者：
Kataoka, K;McGhee, JR;Fujihashi, K
鼻腔免疫是诱导粘膜和全身免疫应答的有效途径。在这项研究中，我们评估了Flt 3配体（FL）的cDNA载体，以提高粘膜免疫或耐受性的潜力。有趣的是，与给予鼻腔OVA加无FL基因的DNA质粒的小鼠相比，避免了耐受性，并且在鼻洗液、粪便提取物和唾液以及血浆中诱导了升高水平的OVA特异性Ab应答。此外，在脾和颈淋巴结中观察到显著水平的OVA特异性CD 4（+）T细胞增殖反应和OVA诱导的IL-4和IL-2产生。此外，FL蛋白在鼻固有层和下颌下腺中显著增加，并且在粘膜组织中CD 11 c（+）CD 8（+）树突状细胞（DC）的频率显著增加。此外，这些DC表达高水平的CD 40、CD 80、CD 86和MHC II类分子。经鼻递送含有OVA的质粒FL导致粘膜诱导和效应位点中的FL表达，并导致扩增的活化淋巴样DC。因此，鼻用质粒FL通过粘膜途径给药时可防止粘膜耐受并增强主动免疫。
Nasal immunization is an effective way to induce both mucosal and systemic immune responses. In this study, we assessed a cDNA vector for Flt3 ligand (FL) for its potential to enhance mucosal immunity or tolerance. Interestingly, tolerance was avoided and elevated levels of OVA-specific Ab responses were induced in nasal washes, fecal extracts, and saliva as well as in plasma when compared with mice given nasal OVA plus DNA plasmid without the FL gene. In addition, significant levels of OVA-specific CD4(+) T cell proliferative responses and OVA-induced IL-4 and IL-2 production were noted in spleen and cervical lymph nodes. Further, marked increases in FL protein occurred in the nasal lamina propria and submandibular glands and the frequencies of CD11c(+)CD8(+) dendritic cells (DCs) significantly increased in the mucosal tissues. Moreover, these DCs expressed high levels of CD40, CD80, CD86, and MHC class II molecules. Nasal delivery of plasmid FL with OVA resulted in FL expression in both mucosal inductive and effector sites and resulted in expanded activated lymphoid DCs. Thus, nasal plasmid FL prevents mucosal tolerance and enhances active immunity when given by a mucosal route.