Induced arginine transport via cationic amino acid transporter‐1 is necessary for human T‐cell proliferation
Induced arginine transport via cationic amino acid transporter‐1 is necessary for human T‐cell proliferation
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DOI：
10.1002/eji.201546047
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发表时间：
2016-01
影响因子：
5.4
通讯作者：
A. Werner;Eva-Maria Amann;V. Schnitzius;A. Habermeier;Claudia Luckner‐Minden;Nadine Leuchtner;J. Rupp-J.
中科院分区：
文献类型：
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作者：
A. Werner;Eva-Maria Amann;V. Schnitzius;A. Habermeier;Claudia Luckner‐Minden;Nadine Leuchtner;J. Rupp-J.
半必需氨基酸精氨酸的可用性是人T淋巴细胞有效功能的基础。主要由髓源性抑制细胞诱导的肿瘤相关精氨酸剥夺是肿瘤免疫逃避T细胞介导的抗肿瘤免疫应答的中心机制。因此，我们假设精氨酸的跨膜转运对T细胞功能至关重要，并研究了哪些转运蛋白负责精氨酸流入原代人T淋巴细胞。在这里，我们表明，通过CD 3和CD 28激活诱导精氨酸转运到原代人T细胞。幼稚和记忆CD 4 + T细胞以及CD 8 + T细胞特异性上调人阳离子氨基酸转运蛋白-1（hCAT-1），在精氨酸饥饿下表达增强且持续。当通过siRNA转染抑制hCAT-1诱导时，精氨酸摄取和细胞增殖受损。总之，我们的研究结果表明，hCAT-1是有效T细胞活化的关键组分，也是调节肿瘤免疫或炎症中适应性免疫反应的新型潜在靶结构。
Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor‐associated arginine deprivation, mainly induced by myeloid‐derived suppressor cells, is a central mechanism of tumor immune escape from T‐cell‐mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T‐cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naïve and memory CD4+ T cells as well as CD8+ T cells specifically upregulated the human cationic amino acid transporter‐1 (hCAT‐1), with an enhanced and persistent expression under arginine starvation. When hCAT‐1 induction was suppressed via siRNA transfection, arginine uptake, and cellular proliferation were impaired. In summary, our results demonstrate that hCAT‐1 is a key component of efficient T‐cell activation and a novel potential target structure to modulate adaptive immune responses in tumor immunity or inflammation.