oligomycins has been researched along with etomoxir* in 1 studies
1 other study(ies) available for oligomycins and etomoxir
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Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function.
Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronic T cells appeared to rely on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to produce ATP for IFNγ synthesis. Check-point blockade, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1-mediated inhibition appears essential for limiting oxidative metabolism linked to effector function in chronic T cells, thereby promoting survival and functional fitness. Topics: Adenosine Triphosphate; Animals; Antibodies, Monoclonal; Antimetabolites, Antineoplastic; B7-H1 Antigen; Cell Lineage; Diazooxonorleucine; DNA-Binding Proteins; Epoxy Compounds; Gene Expression Profiling; Gene Expression Regulation; Glycolysis; Interferon-gamma; Interleukin Receptor Common gamma Subunit; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Oligomycins; Oxidative Phosphorylation; Programmed Cell Death 1 Receptor; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes; Transplantation, Homologous | 2018 |