title: Induced arginine transport via cationic amino acid transporter-1 is necessary for human T-cell proliferation.
abstract: 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.
authors.affiliation: Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Werner
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Amann
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Schnitzius
authors.affiliation: Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Habermeier
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Luckner-Minden
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Leuchtner
authors.affiliation: Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rupp
authors.affiliation: Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Ellen I
authors.initials: EI
authors.lastname: Closs
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.|Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Munder
mesh_terms: D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D027201:Cationic Amino Acid Transporter 1 / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: D027201:Cationic Amino Acid Transporter 1; D034741:RNA, Small Interfering; C420825:SLC7A1 protein, human; D001120:Arginine
keywords: Amino acid transporter; Arginine; Human; T-cell activation