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

Eur J Immunol. 2016 Jan;46(1):92-103. doi: 10.1002/eji.201546047. Epub 2015 Nov 2.


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.

Keywords: Amino acid transporter; Arginine; Human; T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism*
  • Blotting, Western
  • Cationic Amino Acid Transporter 1 / immunology*
  • Cationic Amino Acid Transporter 1 / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Lymphocyte Activation / immunology*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transfection


  • Cationic Amino Acid Transporter 1
  • RNA, Small Interfering
  • SLC7A1 protein, human
  • Arginine