title: Human CD4(+) T cells maintain specific functions even under conditions of extremely restricted ATP production.
abstract: We investigated the energy-adaptive potential of human CD4(+) T cells under conditions of impaired oxidative phosphorylation (OXPHOS) and/or low glucose (inhibiting glycolysis). These cells often encounter these conditions when executing their functions in injured/inflamed tissues, even though T cells themselves require constant and adequate energy supply via ATP. We assessed two specific functions, cytokine synthesis and proliferation, and addressed whether adaptive characteristics also emerged in vivo. In glucose-containing medium, both cytokine production and proliferation were unaffected, even under complete OXPHOS suppression. Only when glucose was also absent were these functions significantly decreased. Partial recovery of OXPHOS and induced glycolysis were crucial for the maintenance of cellular energy supply. Adaptive regulatory mechanisms are clinically relevant because hypoxia up-regulates glycolytic genes but down-regulates OXPHOS genes in vivo. Our data demonstrate an unexpectedly high, clinically relevant adaptive potential of human CD4(+) T cells to maintain specific functions even under severely impaired bioenergetic conditions.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Tripmacher
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.forename: René
authors.initials: R
authors.lastname: Dziurla
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.forename: Kerem
authors.initials: K
authors.lastname: Erekul
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
authors.forename: Miriam
authors.initials: M
authors.lastname: Tschirschmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Scheffold
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D000255:Adenosine Triphosphate / Q000172:deficiency / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D049109:Cell Proliferation; D045303:Cytochromes b / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D014450:Electron Transport Complex III / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D017746:Joint Capsule / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008689:Methacrylates / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D016207:Cytokines; D008689:Methacrylates; D013844:Thiazoles; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D015759:Ionomycin; C030517:myxothiazol; D000255:Adenosine Triphosphate; D045303:Cytochromes b; D014450:Electron Transport Complex III; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate