Long-term antigen exposure deeply modifies metabolic requirements for T cell function
(2018) eLife — Vol. 7, p. e30938 (2018)
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- Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, using a model of T cell transfer in mice, we report that long-term 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 chronically stimulated T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronically stimulated T cells appeared to rely on oxidative phosphorylation (OXPHOS) to produce ATP. PD-1 inhibition, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1 inhibition appears essential for limiting oxidative metabolism linked to effector function in chronically stimulated T cells, thereby promoting survival and functional fitness.
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Citations
Bettonville, M., Weatherly, K., d’Aria, S., Porporato, P. E., Zhang, J., Bousbata, S., Sonveaux, P., & Braun, M. Y. (2018). Long-term antigen exposure deeply modifies metabolic requirements for T cell function. eLife, 7, e30938. https://hdl.handle.net/2078.5/61293 (Original work published 2018)