Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
Clin Immunol. 2010 Sep;136(3):364-74. doi: 10.1016/j.clim.2010.04.019. Epub 2010 Jun 8.
CD1d restricted, alpha-galactosylceramide (alphaGC) responsive invariant (i)NKT cells positively regulate immune responses. Both intravenous and intradermal administered alphaGC are known to activate iNKT cells. iNKT cells become unresponsive to a second intravenous alphaGC 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 alphaGC. Moreover, human skin dendritic cells (DC) took up intradermally injected alphaGC and activated iNKT cells upon migration, while iNKT cells in human skin-draining lymph nodes expanded in response to alphaGC presented either by exogenously added DC or by CD1d positive antigen presenting cells in the lymph nodes. In conclusion, glycolipids such as alphaGC may greatly improve the efficacy of skin immunization strategies, targeting cutaneous and lymph node DC.
CD1d 限制的、α-半乳糖神经酰胺（αGC）反应性不变（i）NKT 细胞正向调节免疫反应。静脉内和皮内给予的 αGC 已知均可激活 iNKT 细胞。iNKT 细胞对第二次静脉内 αGC 注射无反应，而关于皮内给予时潜在失能的数据尚不可用。在这里，对小鼠的两种皮内与两种静脉内注射的比较分析表明，皮内注射可防止 iNKT 细胞失能，并且当与疫苗联合使用时，皮内给予的 αGC 可提供更好的肿瘤保护。此外，人皮肤树突状细胞（DC）摄取皮内注射的 αGC，并在迁移时激活 iNKT 细胞，而人皮肤引流淋巴结中的 iNKT 细胞在响应 αGC 时扩增，该 αGC 由外源添加的 DC 或淋巴结中的 CD1d 阳性抗原呈递细胞呈递。总之，类似 αGC 的糖脂可能会极大地提高针对皮肤和淋巴结 DC 的皮肤免疫策略的疗效。
