IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28null compared to CD4+CD28+T cells
IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28null compared to CD4+CD28+T cells
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DOI：
10.1111/j.1474-9726.2011.00725.x
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发表时间：
2011-10-01
期刊：
影响因子：
7.8
通讯作者：
Lopez-Larrea, Carlos
中科院分区：
文献类型：
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作者：
Alonso-Arias, Rebeca;Moro-Garcia, Marco A.;Lopez-Larrea, Carlos
人类 T 细胞衰老过程中最显着的变化之一是 CD28(null) T 细胞的积累，主要是 CD8+ 和 CD4+ T 细胞。增强这些细胞的功能特性可能很重要，因为它们提供针对慢性感染的抗原特异性防御。最近的研究表明，IL-15 实际上在生理条件下的 CD4 记忆 T 细胞中发挥着重要作用。我们发现，与 CD4+CD28+ T 细胞相比，IL-15 治疗通过优先增殖这些细胞而增加了老年 CD4+CD28(null) T 细胞的频率。 IL-15 诱导 CD4+CD28(null) T 细胞激活表型。虽然IL-15Rα链的表面表达没有增加，但转录因子STAT-5被优先激活。 IL-15 通过增加颗粒酶 B 和穿孔素的 mRNA 转录和储存来增强 CD4+CD28(null) T 细胞的细胞毒特性，以实现细胞溶解效应功能。此外，用IL-15预处理CD4+CD28(null)T细胞对CMV特异性反应中IFN-γ的产生显示出协同效应，而在CD4+CD28+T细胞中未观察到这种效应。 IL-15可以发挥增强CD4+CD28(null)T细胞针对其特定慢性抗原的效应反应的作用。
One of the most prominent changes during T-cell aging in humans is the accumulation of CD28(null) T cells, mainly CD8+ and also CD4+ T cells. Enhancing the functional properties of these cells may be important as they provide an antigen-specific defense against chronic infections. Recent studies have shown that IL-15 does in fact play an appreciable role in CD4 memory T cells under physiological conditions. We found that treatment with IL-15 increased the frequency of elderly CD4+CD28(null) T cells by the preferential proliferation of these cells compared to CD4+CD28+ T cells. IL-15 induced an activated phenotype in CD4+CD28(null) T cells. Although the surface expression of IL-15R alpha-chain was not increased, the transcription factor STAT-5 was preferentially activated. IL-15 augmented the cytotoxic properties of CD4+CD28(null) T cells by increasing both the mRNA transcription and storage of granzyme B and perforin for the cytolytic effector functions. Moreover, pretreatment of CD4+CD28(null) T cells with IL-15 displayed a synergistic effect on the IFN-gamma production in CMV-specific responses, which was not observed in CD4+CD28+ T cells. IL-15 could play a role enhancing the effector response of CD4+CD28(null) T cells against their specific chronic antigens.