The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunization
The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunization
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DOI：
10.1046/j.1365-2567.2002.01488.x
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发表时间：
2002-09-01
期刊：
影响因子：
6.4
通讯作者：
Foldvari, M
中科院分区：
文献类型：
--
作者：
Baca-Estrada, ME;Ewen, C;Foldvari, M
抗原的局部应用诱导抗原特异性体液和细胞免疫应答。在这项研究中，我们研究了是否扩增树突状细胞（DC）的Flt 3配体（Flt 3L）治疗影响诱导免疫反应后经皮免疫。用Flt 3L或磷酸盐缓冲盐水（PBS）腹腔内处理小鼠，并用鸡蛋溶菌酶（HEL）经皮免疫小鼠。Flt 3L处理的小鼠比PBS处理的小鼠产生更低的HEL-specific细胞和体液免疫应答。然而，在霍乱毒素（CT），粘膜和经皮免疫的有效佐剂的存在下，Flt 3L处理的小鼠开发显着更高的细胞和体液免疫应答HEL相比，PBS处理的小鼠。我们评估了CT的免疫调节作用是否是表皮树突状细胞（朗格汉斯细胞; LC）活化的结果。我们的研究结果表明，在8-12小时内局部应用CT，表皮LC细胞失去其树突状形态，并成为圆形的外观。此外，我们观察到增强表达的主要组织相容性复合体（MHC）II类，粘附分子CD 11 c和细胞内粘附分子-1（ICAM-1）。我们的观察结果支持这样的概念，即皮肤中DC的激活状态是调节免疫反应的核心。这些信息与有效的经皮接种策略的设计有关。
Topical application of antigen induces antigen-specific humoral and cellular immune responses. In this study we examined whether expansion of dendritic cells (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune responses following transcutaneous immunization. Mice were treated intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower HEL-specific cellular and humoral immune responses than PBS-treated mice. However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and transcutaneous immunization, Flt3L-treated mice developed significantly higher cellular and humoral immune responses to HEL when compared to PBS-treated mice. We assessed whether the immunomodulatory effects of CT were a result of activation of epidermal dendritic cells (Langerhans' cells; LC). Our results indicate that within 8-12 hr of topical application of CT, epidermal LC cells lose their dendritic morphology and become rounder in appearance. In addition, we observed enhanced expression of major histocompatibility complex (MHC) class II, and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1). Our observations support the concept that the state of activation of DC in the skin is central to the regulation of immune responses. This information is relevant to the design of effective transcutaneous vaccination strategies.