Tripp Christoph H, Sparber Florian, Hermans Ian F, Romani Nikolaus, Stoitzner Patrizia
Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.
J Immunol. 2009 Jun 15;182(12):7644-54. doi: 10.4049/jimmunol.0900134.
APCs, such as dendritic cells (DC), can present glycolipid Ags on CD1d molecules to NKT cells. This interaction activates DC and NKT cells, leading to release of cytokines and enhanced T cell responses. Thus, glycolipid Ags are currently being tested as adjuvants for immunotherapy. We were interested in the interaction of murine skin DC with NKT cells in skin-draining lymph nodes. We observed that all skin DC subsets expressed CD1d upon migration to the lymph nodes. Moreover, skin DC were able to present the synthetic glycolipid Ag alpha-galactosylceramide (alpha-GalCer) to the NKT cell hybridoma DN32.D3. Intradermally injected alpha-GalCer was presented by migratory skin DC and lymph node DC to NKT hybridoma cells in vitro. When we injected alpha-GalCer intradermally into the skin, the numbers of various leukocyte subsets in the draining lymph nodes did not change significantly. However, T and B cells as well as NKT cells up-regulated the activation marker CD69. Coapplication of alpha-GalCer with the tumor model Ag OVA induced strong cytolytic CD8(+) T cell function that could inhibit the growth of B16 melanoma cells expressing OVA. However, mice that were devoid of migratory skin DC developed similar cytotoxic immune responses after intradermal immunization, indicating that skin DC are not required for the adjuvant properties of NKT cell activation and Ag presentation by this immunization route. In conclusion, migratory skin DC are able to interact with NKT cells; however, intradermally applied glycolipids are presented predominantly by lymph node DC to NKT cells.
抗原呈递细胞（APCs），如树突状细胞（DC），可将糖脂抗原呈递于CD1d分子上给自然杀伤T细胞（NKT细胞）。这种相互作用激活DC和NKT细胞，导致细胞因子释放并增强T细胞反应。因此，糖脂抗原目前正作为免疫治疗佐剂进行测试。我们对小鼠皮肤DC与引流皮肤的淋巴结中的NKT细胞之间的相互作用感兴趣。我们观察到，所有皮肤DC亚群迁移至淋巴结后均表达CD1d。此外，皮肤DC能够将合成糖脂抗原α-半乳糖神经酰胺（α-GalCer）呈递给NKT细胞杂交瘤DN32.D3。皮内注射的α-GalCer在体外被迁移的皮肤DC和淋巴结DC呈递给NKT杂交瘤细胞。当我们将α-GalCer皮内注射到皮肤中时，引流淋巴结中各种白细胞亚群的数量没有明显变化。然而，T细胞、B细胞以及NKT细胞上调了激活标志物CD69。α-GalCer与肿瘤模型抗原OVA共同应用可诱导强烈的细胞毒性CD8(+) T细胞功能，从而抑制表达OVA的B16黑色素瘤细胞的生长。然而，缺乏迁移性皮肤DC的小鼠在皮内免疫后也产生了类似的细胞毒性免疫反应，这表明通过这种免疫途径激活NKT细胞和抗原呈递的佐剂特性并不需要皮肤DC。总之，迁移性皮肤DC能够与NKT细胞相互作用；然而，皮内应用的糖脂主要由淋巴结DC呈递给NKT细胞。
