Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining.

Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining.
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DOI:
10.1084/jem.20011786
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发表时间:
2002-03-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Brenner MB
Brenner MB
中科院分区:
其他
文献类型:
--
作者:
Gumperz JE;Miyake S;Yamamura T;Brenner MB

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已知CD 1d限制性自然杀伤(NK)T细胞有效地分泌辅助性T细胞(Th)1和Th 2细胞因子并介导细胞溶解,但尚不清楚这些相反的功能活动是如何调节的。使用脂质抗原负载的CD 1d四聚体,我们已经区分了两个子集的CD 1d限制性T细胞在新鲜外周血中不同的细胞因子的产生和细胞毒性激活。一个亚群是CD 4 −,选择性地产生Th 1细胞因子干扰素γ和肿瘤坏死因子α,并表达NKG 2d,这是一种与微生物感染和肿瘤细胞溶解相关的标志物。该亚群在暴露于白细胞介素(IL)-2或IL-12后上调穿孔素。相反,CD 4 + CD 1d限制性NKT细胞有效地产生Th 1和Th 2细胞因子,上调穿孔素响应佛波醇肉豆蔻酸酯乙酸酯和离子霉素的刺激,但不是IL-2或IL-12,并可以诱导表达CD 95 L。此外,对于两种CD 1d限制性NKT细胞亚群,我们发现抗原刺激诱导细胞因子产生,但不诱导穿孔素表达,而暴露于炎症因子增强穿孔素表达,但不刺激细胞因子产生。这些结果表明,CD 1d限制性T细胞在肿瘤排斥反应,自身免疫性疾病和微生物感染中的各种活动可能是由功能不同的亚群激活引起的,并且炎症和抗原刺激可能影响不同的效应器功能。
CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen–loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activation. One subset, which was CD4−, selectively produced the Th1 cytokines interferon γ and tumor necrosis factor α, and expressed NKG2d, a marker associated with cytolysis of microbially infected and neoplastic cells. This subset up-regulated perforin after exposure to interleukin (IL)-2 or IL-12. In contrast, CD4+ CD1d-restricted NKT cells potently produced both Th1 and Th2 cytokines, up-regulated perforin in response to stimulation by phorbol myristate acetate and ionomycin but not IL-2 or IL-12, and could be induced to express CD95L. Further, for both CD1d-restricted NKT cell subsets, we found that antigenic stimulation induced cytokine production but not perforin expression, whereas exposure to inflammatory factors enhanced perforin expression but did not stimulate cytokine production. These results show that the various activities of CD1d-restricted T cells in tumor rejection, autoimmune disease, and microbial infections could result from activation of functionally distinct subsets, and that inflammatory and antigenic stimuli may influence different effector functions.
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