Memory CD8+ T cells use cell intrinsic lipolysis to support the metabolic programming necessary for development

By David O’Sullivan, G. V. D. van der Windt, Stanley Ching-Cheng Huang, Jonathan D. Curtis, Chih-Hao Chang, Michael D. Buck, J. Qiu, A. Smith, W. Lam, Lisa M DiPlato and 4 more. Immunity, 2014

699 citations recorded by the source corpus.

Summary Generation of CD8+ memory T (TM) cells requires metabolic reprogramming that is characterized by enhanced mitochondrial fatty acid oxidation (FAO). However, where the fatty acids (FA) that fuel this process come from remains unclear. We found that while CD8+ TM cells engaged higher levels of FAO, they acquired substantially fewer long-chain FA from their external environment than CD8+ effector T (TE) cells. Rather than using extracellular FA directly, TM cells used extracellular glucose to support FAO and oxidative phosphorylation (OXPHOS), suggesting that lipids must be synthesized to generate the substrates needed for FAO. We have demonstrated that TM cells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and TM cell development. Our observations link LAL to metabolic reprogramming in lymphocytes and show that cell intrinsic lipolysis is deterministic for TM cell fate.

Subfields: Genetics, Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/492b58f05031162c053045902b84923fc8676178

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. C. V. Dang
2. Russell G. Jones
3. B. Altman
4. Zachary E. Stine

In Immunology

1. Erika L. Pearce
2. Russell G. Jones
3. G. V. D. van der Windt
4. C. V. Dang
5. C. Piccirillo
6. E. Shevach
7. Navdeep S. Chandel
8. Michael D. Buck

In Surgery

1. C. V. Dang
2. Russell G. Jones
3. Erika L. Pearce
4. B. Viollet

Citations in the corpus

• MYC, Metabolism, and Cancer. (2015, background): “Intriguingly, in the case of resting memory T cells, a major source of energy for homeostasis is a futile cycle of oxidation of de novo–synthesized lipids (72).”
• Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “CD8+ Te cells also import fatty acids for biosynthesis during rapid replication, but CD8+ Tm cells rely on glucose to synthesize their fatty acids, which are subsequently broken down by cell-intrinsic lipolysis to provide substrates for FAO (72).”
• The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. (2015, methodology): “) with 100 mg 2-NBDG/mouse 15 min prior to analysis (O’Sullivan et al., 2014).”