Miyake Sachiko
Department of Immunology, National Institute of Neuroscience, NCNP.
Nihon Rinsho Meneki Gakkai Kaishi. 2006 Feb;29(1):27-36. doi: 10.2177/jsci.29.27.
iNKT cells are a unique subset of CD1-restricted T lymphocytes that express T cell receptor (TCR) and some NK receptors. iNKT cells express an invariant TCRalpha chain composed of Valpha14-Jalpha18 segments in mice and Valpha24-Jalpha18 segments in humans associated with TCRbeta chains using a restricted set of Vbeta. iNKT cells recognize glycolipid antigens such as alpha-galactosylceramide (alpha-GC) presented by CD1d, non-pormorphic MHC class I-like molecule, and rapidly secrete large amounts of cytokines including IL-4 and IFN-gamma upon activation. Due to its potent ability to produce a variety of cytokines, iNKT cells are involved in a various kinds of immunoregulation. iNKT cells play a regulatory role in some disease models such as type I diabetes in NOD mice. In contrast, iNKT cells exaggerate the pathogenesis such as arthritis, allergic airway inflammation and atherosclerosis. In addition, iNKT cells are an attractive target for immunotherapy because several different synthetic glycolipid antigens to modify the function of iNKT cells are available. In this review, we examine the potential roles of NKT cells in the pathogenesis of a variety of diseases including autoimmunity , allergy, infection and cancer. Additionally, we discuss on the recent advances in glycolipid therapy for these disease models.
自然杀伤T细胞(iNKT细胞)是CD1限制性T淋巴细胞的一个独特亚群,表达T细胞受体(TCR)和一些自然杀伤(NK)受体。iNKT细胞表达一种恒定的TCRα链,在小鼠中由Vα14-Jα18片段组成,在人类中由Vα24-Jα18片段组成,并使用一组有限的Vβ与TCRβ链相关联。iNKT细胞识别由CD1d(一种非多态性的MHC I类样分子)呈递的糖脂抗原,如α-半乳糖神经酰胺(α-GC),并在激活后迅速分泌大量细胞因子,包括白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)。由于其产生多种细胞因子的强大能力,iNKT细胞参与了各种免疫调节。iNKT细胞在一些疾病模型中发挥调节作用,如非肥胖糖尿病(NOD)小鼠的I型糖尿病。相反,iNKT细胞会加剧某些疾病的发病机制,如关节炎、过敏性气道炎症和动脉粥样硬化。此外,iNKT细胞是免疫治疗的一个有吸引力的靶点,因为有几种不同的合成糖脂抗原可用于调节iNKT细胞的功能。在这篇综述中,我们研究了NKT细胞在包括自身免疫、过敏、感染和癌症在内的多种疾病发病机制中的潜在作用。此外,我们还讨论了针对这些疾病模型的糖脂疗法的最新进展。