Human CD4(+) T cells maintain specific functions even under conditions of extremely restricted ATP production.
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.
Tripmacher
Robert
R
Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany.
Gaber
Timo
T
Dziurla
René
R
Häupl
Thomas
T
Erekul
Kerem
K
Grützkau
Andreas
A
Tschirschmann
Miriam
M
Scheffold
Alexander
A
Radbruch
Andreas
A
Burmester
Gerd-Rüdiger
GR
Buttgereit
Frank
F
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
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