Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers.
Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers.
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DOI：
10.1084/jem.192.5.741
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发表时间：
2000-09-04
期刊：
影响因子：
--
通讯作者：
Kronenberg M
中科院分区：
文献类型：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
一组主要的自然杀伤（NK）T细胞表达一种对脂聚糖α-半乳糖神经酰胺（α-GalCer）具有特异性的不变Vα14+ T细胞受体（TCR），由CD 1d呈递。这些细胞可能具有重要的免疫调节功能，但由于缺乏合适的试剂在体内追踪它们，因此对其生物学的理解受到阻碍。在这里，我们表明负载α-GalCer的小鼠CD 1d四聚体是用于鉴定Vα14+ NK T细胞的敏感且高度特异性的试剂。使用这些四聚体，我们发现α-GalCer特异性T淋巴细胞的分布比以前认识到的更广泛，淋巴结和肠道中存在大量NK1.1-但四聚体结合的T细胞。注射α-GalCer导致肝脏和大部分脾脏中几乎所有NK T细胞在2 h内产生干扰素γ和白细胞介素4。这些细胞大多数在5小时内消失，1周后不再出现。奇怪的是，四聚体阳性的胸腺细胞不迅速合成细胞因子，也不经历脂质抗原刺激后细胞数量的减少，尽管它们表达相等的TCR水平。总之，本文提供的数据表明，α-GalCer特异性NK T细胞对抗原刺激产生独特且高度区室化的应答。
A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer–specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1− but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer–specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.
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