Targeting memory T cell metabolism to improve immunity
Mauro Corrado, Erika L. Pearce
Mauro Corrado, Erika L. Pearce
Published January 4, 2022
Citation Information: J Clin Invest. 2022;132(1):e148546. https://doi.org/10.1172/JCI148546.
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Review Series

Targeting memory T cell metabolism to improve immunity

Abstract

Vaccination affords protection from disease by activating pathogen-specific immune cells and facilitating the development of persistent immunologic memory toward the vaccine-specific pathogen. Current vaccine regimens are often based on the efficiency of the acute immune response, and not necessarily on the generation of memory cells, in part because the mechanisms underlying the development of efficient immune memory remain incompletely understood. This Review describes recent advances in defining memory T cell metabolism and how metabolism of these cells might be altered in patients affected by mitochondrial diseases or metabolic syndrome, who show higher susceptibility to recurrent infections and higher rates of vaccine failure. It discusses how this new understanding could add to the way we think about immunologic memory, vaccine development, and cancer immunotherapy.

Authors

Mauro Corrado, Erika L. Pearce

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Figure 1

Metabolic pathways in naive, effector, and memory T cells.

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Metabolic pathways in naive, effector, and memory T cells. (A) Schematic...
(A) Schematic of the dynamic of T cell immune response upon primary and secondary infection, depicting T cell differentiation from Tn, to Teff, and Tm cells. (B) Metabolic features of naive, effector, and memory T cells. Briefly, naive T cells are metabolically quiescent, relying on basal levels of OXPHOS for their energetic needs. Upon activation, effector T cells become highly metabolically active, increasing their substrate uptake together with glycolysis and OXPHOS. During memory T cell differentiation, metabolism rewires to a more quiescent state in which FAO and OXPHOS sustain T cell survival and energetic requirements. (C) Illustrations of the different mitochondrial morphology and ultrastructure observed in T cell subtypes. Mouse Tn cells and in vitro–differentiated IL-15 Tm cells show elongated mitochondria, while in vitro–differentiated IL-2 Teff cells display fragmented mitochondria. IL-2 Teff cells show wider cristae structure compared with the tight and elongated structure observed in IL-15 Tm cells. FAS, fatty acid synthesis.