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Updated: Jul 30, 2026
Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
Published on: June 21, 2018
Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells
Laura Barbieri1,2,3, Pedro Veliça1, Paulo A Gameiro4,5
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Introduction:
CD8+ T cells infiltrate virtually every tissue to find and destroy infected or mutated cells. They often traverse varying oxygen levels and nutrient-deprived microenvironments. High glycolytic activity in local tissues can result in significant exposure of cytotoxic T cells to the lactate metabolite. Lactate has been known to act as an immunosuppressor, at least in part due to its association with tissue acidosis.
Methods:
To dissect the role of the lactate anion, independently of pH, we performed phenotypical and metabolic assays, high-throughput RNA sequencing, and mass spectrometry, on primary cultures of murine or human CD8+ T cells exposed to high doses of pH-neutral sodium lactate.
Results:
The lactate anion is well tolerated by CD8+ T cells in pH neutral conditions. We describe how lactate is taken up by activated CD8+ T cells and can displace glucose as a carbon source. Activation in the presence of sodium lactate significantly alters the CD8+ T cell transcriptome, including the expression key effector differentiation markers such as granzyme B and interferon-gamma.
Discussion:
Our studies reveal novel metabolic features of lactate utilization by activated CD8+ T cells, and highlight the importance of lactate in shaping the differentiation and activity of cytotoxic T cells.
