title: Adjuvant induced glucose uptake by activated T cells is not correlated with increased survival.
abstract: Authors contributed equally to this manuscript Natural adjuvants, such as bacterial lipopolysaccharide (LPS), activate antigen presenting cells via Toll-like receptors and, indirectly, increase the survival of antigen-activated T cells. The molecular mechanisms leading to increased survival remain poorly defined. Because T cell clonal expansion leads to high energy demands, we hypothesized that increased glucose uptake and/or utilization in adjuvant-activated T cells could be important molecular event(s) that would lead to adjuvant-associated T cell survival advantage. Using a fluorescent analog of 2-deoxyglucose, 2-NBDG, we measured glucose accumulation and rate of uptake in T cells from mice treated with antigen in the absence or presence of LPS. Although adjuvant activated T cells increased the accumulation of 2-NBDG, the rate of uptake was unchanged compared to cells activated with only antigen. Furthermore, glucose transport inhibitors, cytochalasin B or phloretin, decreased the accumulation of glucose in adjuvant-treated T cells, but this decrease did not impair adjuvant-associated survival advantages. Together, these data indicate that increased glucose uptake through glucose transporters is not required for increased survival of activated T cells.
authors.affiliation: Institute for Cellular Therapeutics, University of Louisville School of Medicine, 570, S. Preston Street, Louisville, KY 40202, USA.
authors.forename: Sadhak
authors.initials: S
authors.lastname: Sengupta
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Vitale
authors.forename: Paula M
authors.initials: PM
authors.lastname: Chilton
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mitchell
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D005947:Glucose / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010693:Phloretin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D004768:Enterotoxins; D008070:Lipopolysaccharides; C045400:6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminoglucose; C026066:enterotoxin A, Staphylococcal; D003571:Cytochalasin B; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; D005944:Glucosamine; D010693:Phloretin