Abstract
Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2) regulates fatty acid oxidation (FAO) by inhibiting carnitine palmitoyltransferase 1 (CPT1), a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen-specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses.
Highlights
CD8+ T cells are the primary population responsible for protective immunity to infection with intracellular pathogens and cancer
In order to evaluate whether acetyl CoA carboxylase 2 (ACC2) regulates cellular fatty acid oxidation (FAO) in T cells, we measured in vitro oxidation of 3H-palmitate to 3H2O with CD8+ T cells
No differences were observed in mitochondrial mass between WT and ACC2ΔT CD8+ T cells, and interestingly, ACC2ΔT CD8+ T cells exhibited only slightly altered FAO compared to WT CD8+ T cells in naïve conditions (Fig 1C), suggesting only marginal contributions by ACC2 to FAO regulation in CD8+ T cells
Summary
CD8+ T cells are the primary population responsible for protective immunity to infection with intracellular pathogens and cancer. Upon antigen (Ag) encounter, CD8+ T cells undergo an expansion phase and an effector phase, followed by a contraction phase, as a result of the orchestration of cell-extrinsic and-intrinsic factors. Only a small subset of cells survives to differentiate into memory cells that ensure faster and more efficient immune protection against later infection. Proliferating effector T cells switch to glycolysis, while quiescent naïve or memory T cells predominantly utilize oxidative phosphorylation (OXPHOS) by using glucose, amino acids, and fatty acids as carbon sources. A recent study suggests that the superior capacity of memory T cells for fatty acid oxidation (FAO) supports their long-term survival [1]. Despite recent advances in PLOS ONE | DOI:10.1371/journal.pone.0137776. Despite recent advances in PLOS ONE | DOI:10.1371/journal.pone.0137776 September 14, 2015
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