IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells
IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells
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DOI：
10.1073/pnas.092675799
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发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Weng, NP
中科院分区：
文献类型：
--
作者：
Liu, KB;Catalfamo, M;Weng, NP
CD 8（+）记忆T细胞的产生需要通过T细胞受体（TCR）的抗原刺激;然而，CD 8+记忆T细胞的维持似乎是由细胞因子如IL-15以TCR非依赖性方式介导的。与TCR诱导的活化相比，对IL-15作用的机制知之甚少。我们在此报告了记忆表型CD 8（+）T细胞对IL-15或TCR（抗CD 3）刺激的反应的比较和动力学分析。这两种刺激在记忆表型CD 8（+）T细胞中诱导高度相似的反应，如通过细胞增殖、基因表达变化、效应分子（IFN γ、肿瘤坏死因子β、颗粒酶B和穿孔素）的合成和细胞毒性的诱导所测量的。通过cDNA微阵列分析发现，在IL-15和抗CD 3刺激后，CD 8（+）记忆T细胞中表达发生变化的189个基因/表达序列标签（EST）中，77%的基因/EST表现出高度相似的表达模式IL-15和抗CD 31处理的细胞，IL-15和抗CD 3处理后，分别只有16%和7%的基因/EST差异表达。这些结果表明，IL-15和抗CD 3刺激诱导非常相似的基因表达和效应子功能。因此，IL-15不仅作为一个关键的生长因子，而且作为一个CD 8（+）记忆T细胞的效应功能的抗原非依赖性激活剂。
Generation of CD8(+) memory T cells requires antigenic stimulation through T cell receptor (TCR); however, maintenance of CD8+ memory T cells seems to be mediated by cytokines, such as IL-15, in a TCR-independent manner. Compared with the TCR-induced activation, less is known about the mechanisms of IL-15 action. We report here a comparative and kinetic analysis of the responses of memory phenotype CD8(+) T cells to IL-15 or TCR (anti-CD3) stimulation in vitro. These two stimuli induce highly similar responses in memory phenotype CD8(+) T cells as measured by cellular proliferation, gene expression changes, synthesis of effector molecules (IFNgamma, tumor necrosis factor beta, granzyme B, and perforin), and induction of cytotoxicity. From 189 genes/expressed sequence tags (ESTs) whose expression changed in CD8(+) memory T cells after IL-15 and anti-CD3 stimulation identified by cDNA microarray analysis, 77% of the genes/ESTs exhibit a highly similar pattern of expression between IL-15 and anti-CD31-treated cells, and only 16% and 7% of the genes/ESTs are differentially expressed in response to IL-15 and anti-CD3 treatments, respectively. These results show that IL-15 and anti-CD3 stimulation induced remarkably similar gene expression and effector function. Thus, IL-15 acts not only as a crucial growth factor but also as an antigen-independent activator of effector functions for CD8(+) memory T cells.