Interleukin-12 and interleukin-2-induced invariant natural killer T-cell cytokine secretion and perforin expression independent of T-cell receptor activation.
Interleukin-12 and interleukin-2-induced invariant natural killer T-cell cytokine secretion and perforin expression independent of T-cell receptor activation.
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Interleukin-12 和 interleukin-2 诱导不变的自然杀伤 T 细胞细胞因子分泌和穿孔素表达，与 T 细胞受体激活无关。
DOI：
10.1046/j.1365-2567.2003.01701.x
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发表时间：
2003
期刊：
影响因子：
6.4
通讯作者：
Wilson,SBrian
中科院分区：
文献类型：
--
作者：
Hou,Runhua;Goloubeva,Olga;Neuberg,DonnaS;Strominger,JackL;Wilson,SBrian
表达恒定 Vα24-Jα15 T 细胞受体 (TCR) 的人类恒定自然杀伤 (iNK) T 细胞被认为是自身免疫和肿瘤监测的重要调节因子。已知存在两个主要的 iNK T 细胞亚群 CD4+ 或 CD4−CD8−，但 CD4 表达的体内重要性尚不清楚。由于白介素-12 (IL-12) 是一种关键的 iNK T 细胞激活细胞因子，因此检查了 IL-12 加或减 T 细胞生长因子 IL-2 对大量 CD4+ 与 CD4−CD8−iNK T 细胞克隆的影响。引人注目的是，在没有TCR刺激的情况下，IL-12和IL-2显着激活iNK T细胞分泌IL-4、干扰素-γ和粒细胞-巨噬细胞集落刺激因子，并上调穿孔素表达。此外，IL-2 和 IL-12 治疗导致 CD4-CD8-克隆细胞凋亡优先增加。因此，独立于 TCR 激活，IL-2 和 IL-12 可以直接激活 iNK T 细胞，并为 CD4+iNK T 细胞群提供选择性优势。
Human invariant natural killer (iNK) T cells expressing an invariant Vα24‐Jα15 T‐cell receptor (TCR) are thought to be important regulators of autoimmunity and tumour surveillance. Two major subsets of iNK T cells, CD4+or CD4−CD8−are known to exist, but thein vivoimportance of CD4 expression is unclear. Since interleukin‐12 (IL‐12) is a key iNK T‐cell‐activating cytokine, the effect of IL‐12 plus or minus the T‐cell growth factor IL‐2 on a large panel of CD4+versus CD4−CD8−iNK T‐cell clones was examined. Strikingly, IL‐12 and IL‐2 significantly activated iNK T cells to secrete IL‐4, interferon‐γ and granulocyte–macrophage colony‐stimulating factor, and up‐regulated perforin expression in the absence of TCR stimulation. Furthermore, IL‐2 and IL‐12 treatment resulted in a preferential increase in apoptosis of CD4−CD8−clones. Thus, independent of TCR activation, IL‐2 and IL‐12 can directly activate iNK T cells and provide a selective advantage to the CD4+iNK T‐cell population.