Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress.
Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Microbiology and Immunology, School of Medicine, University of Louisville, KY 40292.
E S
ES
Miller
J C
JC
Klinger
C
C
Akin
D A
DA
Koebel
G
G
Sonnenfeld
D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D007016:Hypophysectomy; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011433:Propranolol / Q000494:pharmacology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013312:Stress, Physiological / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D003847:Deoxyglucose; D011433:Propranolol; D003345:Corticosterone