Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset.
Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset.
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DOI：
10.1007/s00251-016-0930-1
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发表时间：
2016-08
期刊：
影响因子：
3.2
通讯作者：
Kumar V
中科院分区：
文献类型：
--
作者：
Dasgupta S;Kumar V
II型自然杀伤T细胞（NKT）是先天性样CD1d限制性淋巴细胞的一个亚群，对脂质抗原有反应。与表达半恒定T细胞受体（TCR）的I型NKT细胞不同，II型NKT细胞表达更广泛的TCR库。此外，其他特征，例如在人类与小鼠中它们相较于I型细胞的优势、其配体的性质、CD1d/脂质/TCR结合以及对免疫反应的调节，都将II型NKT细胞与I型NKT细胞区分开来。有趣的是，正是II型NKT细胞的自身脂质反应性有助于确定它们在健康和疾病中的生理作用。硫化物作为小鼠中CD1d限制性II型NKT细胞的主要抗原之一的发现，对这些细胞的特性描述起到了重要作用，包括TCR库、CD1d/脂质/TCR复合物的晶体结构及其功能。随后，来自内源性和微生物源的其他几种糖脂和磷脂已被证明可激活II型NKT细胞。给予硫化物或溶血磷脂酰胆碱（LPC）后，特定II型NKT细胞亚群的激活导致与I型NKT细胞失活、常规树突状细胞相关的主要免疫调节途径的参与以及促炎性Th1/Th17细胞的抑制。因此，II型NKT细胞已被证明在自身免疫性疾病、炎症性肝病和癌症中具有免疫抑制作用。鉴于它们在人类中的相对患病率高于I型NKT细胞，了解它们的生物学对于健康和疾病至关重要。
Type II natural killer T cells (NKT) are a subset of the innate-like CD1d-restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease.
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