Attenuation of invariant Natural Killer T-cell anergy induction through intradermal delivery of α-galactosylceramide
Attenuation of invariant Natural Killer T-cell anergy induction through intradermal delivery of α-galactosylceramide
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DOI：
10.1016/j.clim.2010.04.019
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发表时间：
2010-09-01
影响因子：
8.6
通讯作者：
Scheper, Rik J.
中科院分区：
文献类型：
--
作者：
Bontkes, Hetty J.;Moreno, Maria;Scheper, Rik J.
CD1d受限，α -半乳糖神经酰胺（α GC）反应不变性(i)NKT细胞积极调节免疫反应。已知静脉注射和皮内注射α GC都能激活iNKT细胞。iNKT细胞对第二次静脉注射α - GC无反应，而皮内给药的潜在能量尚无数据。在这里，对小鼠进行两次皮内注射和两次静脉注射的比较分析表明，皮内注射可以阻止iNKT细胞的能量，当与疫苗联合使用时，皮内给药的α GC提供了更好的肿瘤保护。此外，人皮肤树突状细胞（DC）接受皮内注射的α - GC并在迁移时激活iNKT细胞，而人皮肤引流淋巴结中的iNKT细胞对外源添加的DC或淋巴结中CD1d阳性抗原呈递细胞的α - GC呈扩增反应。综上所述，α - GC等糖脂可以显著提高皮肤免疫策略的效果，针对皮肤和淋巴结DC。(C) 2010爱思唯尔公司版权所有。
CD1d restricted, alpha-galactosylceramide (alpha GC) responsive invariant (i)NKT cells positively regulate immune responses. Both intravenous and intradermal administered alpha GC are known to activate iNKT cells. iNKT cells become unresponsive to a second intravenous alpha GC injection, whereas no data are available regarding potential anergy upon intradermal administration. Here, comparative analysis of two intradermal versus two intravenous injections in mice demonstrated that iNKT cell anergy was prevented by intradermal injection and when combined with a vaccine, superior tumor protection afforded by intradermally administered alpha GC. Moreover, human skin dendritic cells (DC) took up intradermally injected alpha GC and activated iNKT cells upon migration, while iNKT cells in human skin-draining lymph nodes expanded in response to alpha GC presented either by exogenously added DC or by CD1d positive antigen presenting cells in the lymph nodes. In conclusion, glycolipids such as alpha GC may greatly improve the efficacy of skin immunization strategies, targeting cutaneous and lymph node DC. (C) 2010 Elsevier Inc. All rights reserved.