Induced arginine transport via cationic amino acid transporter‐1 is necessary for human T‐cell proliferation

• Published in: European journal of immunology 2016-01, Vol.46 (1), p.92-103
• Main Authors: Werner, Anke, Amann, Eva, Schnitzius, Vanessa, Habermeier, Alice, Luckner‐Minden, Claudia, Leuchtner, Nadine, Rupp, Johanna, Closs, Ellen I., Munder, Markus
• Format: Article
• Language: English
• Subjects: Amino acid transporter; Arginine; Arginine - metabolism; Blotting, Western; Cationic Amino Acid Transporter 1 - immunology; Cationic Amino Acid Transporter 1 - metabolism; Cell Proliferation; Cells, Cultured; Human; Humans; Lymphocyte Activation - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transfection; T‐cell activation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546047

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.