Extracellular Lactate: A Novel Measure of T Cell Proliferation.

Abstract

Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodelling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. Here we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods of determining T cell responses, namely 3H-thymidine incorporation and the use of cell proliferation tracking dyes. Furthermore, we demonstrate the utility of measuring lactate as a read-out in conventional suppression assays and high throughput peptide screening assays. Extracellular lactate was stably produced over 7 days and results were reproducibly performed over several freeze-thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable and easy to implement research tool for measuring T cell responses and cellular metabolic changes in vitro.