Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceram ides
Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceram ides
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DOI：
10.1073/pnas.0407488102
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发表时间：
2005-03-01
影响因子：
11.1
通讯作者：
Porcelli, SA
中科院分区：
文献类型：
--
作者：
Yu, KOA;Im, JS;Porcelli, SA
α-半乳糖基神经酰胺KRN 7000的一种形式，激活CD 1d限制性Valpha 14不变（Valpha 14 i）自然杀伤（NK）T细胞，并启动多种下游免疫反应。我们报告说，用较短的不饱和脂肪酸取代KRN 7000的C26：0 N-酰基链改变了Valpha 14 i NKT细胞活化的结果。一种含有二不饱和C20脂肪酸（C20：2）的类似物有效诱导了T辅助细胞2型偏向性细胞因子应答，IFN-γ产生减少，Valpha 14 i NKT细胞扩增减少。C20：2也表现出比KRN 7000更不严格的负载到CD 1d上的要求，这表明了这种脂质的免疫调节特性的机制。由这类Valpha 14 i NKT细胞激动剂引起的差异细胞应答可以证明在免疫学应用中是有用的。
A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14-invariant (Valpha14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty acid (C20:2) potently induced a T helper type 2-biased cytokine response, with diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2 also exhibited less stringent requirements for loading onto CD1d than KRN7000, suggesting a mechanism for the immunomodulatory properties of this lipid. The differential cellular response elicited by this class of Valpha14i NKT cell agonists may prove to be useful in immunotherapeutic applications.