IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells
IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells
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DOI：
10.4049/jimmunol.175.2.755
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
van Lier, RAW
中科院分区：
文献类型：
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作者：
Alves, NL;Arosa, FA;van Lier, RAW
人初始CD 8（+）T细胞能够以Ag非依赖性方式对IL-7和IL-15应答。尽管IL-7在很大程度上维持CD 8（+）T细胞处于初始表型，但IL-15将这些细胞驱动为效应子表型，其特征在于，在其他特征中，共刺激分子CD 28的下调。我们评估了CD 4（+）Th细胞衍生的共同γ链细胞因子IL-21对苦参碱诱导的初始CD 8（+）T细胞活化的影响。用IL-21刺激不诱导分裂，并且仅略微增加IL-15诱导的幼稚CD 8（+）T细胞的增殖。然而，引人注目的是，IL-15诱导的CD 28下调完全被IL-21在蛋白质和转录水平上阻止。与IL-15刺激的T细胞相比，通过组合的TCR/CD 3和CD 28触发的后续刺激导致IL-15/IL-21刺激的细胞中IL-2和IFN-γ的产生显著更高。我们的数据显示，IL-21调节经历IL-15诱导的稳态增殖的初始CD 8（+）T细胞的表型，并保持其对CD 28配体的反应性。
Human naive CD8(+) T cells are able to respond in an Ag-independent manner to IL-7 and IL-15. Whereas IL-7 largely maintains CD8(+) T cells in a naive phenotype, IL-15 drives these cells to an effector phenotype characterized, among other features, by down-regulation of the costimulatory molecule CD28. We evaluated the influence of the CD4(+) Th cell-derived common gamma-chain cytokine IL-21 on cytokine-induced naive CD8(+) T cell activation. Stimulation with IL-21 did not induce division and only slightly increased IL-15-induced proliferation of naive CD8(+) T cells. Strikingly, however, IL-15-induced down-modulation of CD28 was completely prevented by IL-21 at the protein and transcriptional level. Subsequent stimulation via combined TCR/CD3 and CD28 triggering led to a markedly higher production of IL-2 and IFN-gamma in IL-15/IL-21-stimulated cells compared with IL-15-stimulated T cells. Our data show that IL-21 modulates the phenotype of naive CD8(+) T cells that have undergone IL-15 induced homeostatic proliferation and preserves their responsiveness to CD28 ligands.