The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, USA.
Mol Immunol. 2013 Sep;55(2):179-81. doi: 10.1016/j.molimm.2012.10.016. Epub 2012 Nov 20.
An increasing number of lipid mediators have been identified as key modulators of immunity. Among these is a family of glycolipids capable of cellular uptake, loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells are particularly interesting because they bridge innate and adaptive immunity by coordinating the early events of dendritic cell maturation, recruitment of NK cells, CD4 and CD8 T cells, and B cells at the site of microbial injury. As such, their therapeutic manipulation could be of the greatest interest in vaccine design or active immunotherapy. However, the use of NKT cells as cellular adjuvant of immunity in the clinic will require a better knowledge of the pharmacology of lipid agonists in order to optimize their action and avoid potential unseen off-target effects. We have been studying extracellular transport and cellular uptake of NKT agonists for the past few years. This field is confronted to a very limited prior knowledge and a small set of usable tools. New technology must be put in place and adapted to answering basic immunology questions related to NKT cells. The intimate link between the pharmacology of glycolipids and lipid metabolism makes us believe that great variations of bioactivity could be seen in the general population when NKT agonists are used therapeutically.
越来越多的脂质介质已被确定为免疫的关键调节剂。其中有一类糖脂能够被细胞摄取，负载到 MHC 样分子 CD1d 上，并刺激 NKT 细胞。NKT 细胞特别有趣，因为它们通过协调树突状细胞成熟的早期事件、NK 细胞、CD4 和 CD8 T 细胞以及微生物损伤部位的 B 细胞的募集，将先天免疫和适应性免疫联系起来。因此，它们的治疗性操作在疫苗设计或主动免疫治疗中可能具有最大的意义。然而，为了优化其作用并避免潜在的未知的脱靶效应，将 NKT 细胞用作免疫的细胞佐剂，在临床上需要更好地了解脂质激动剂的药理学。在过去的几年中，我们一直在研究 NKT 激动剂的细胞外转运和细胞摄取。这个领域面临着非常有限的先验知识和一小部分可用的工具。必须采用新技术，并使其适应回答与 NKT 细胞相关的基本免疫学问题。糖脂的药理学和脂质代谢之间的密切联系使我们相信，当 NKT 激动剂在治疗上被使用时，在普通人群中可能会看到很大的生物活性变化。
