title: Exogenous amino acids are essential for interleukin-7 induced CD8 T cell growth. [corrected].
abstract: IL-7 signalling is important in regulating both survival and cellular size (growth) of T cells. While glucose metabolism has previously been implicated in the mechanism of IL-7 induced survival and growth, the role of amino acids has not before been reported. Here, we show IL-7 dependent T cell survival does not require either exogenous glucose or amino acids. In contrast, maintenance of cell size and IL-7 induced growth were specifically dependent on amino acids. Furthermore, cellular amino acid uptake was implicated in the mechanism of IL-7 induced growth. Analysis of IL-7 regulated gene expression revealed that neutral and cationic amino acid transporters were specific transcriptional targets of IL-7 signalling. In contrast, none of the four glucose transporters expressed in T cells were modulated. Taken together, these data reveal for the first time the central importance of amino acid homeostasis for IL-7 regulated T cell growth.
authors.affiliation: Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Pearson
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Benedict
authors.initials: B
authors.lastname: Seddon
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D027261:Fusion Regulatory Protein-1; D051246:Glucose Transport Proteins, Facilitative; D015851:Interleukin-7; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; D005947:Glucose