Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels

Clin Immunol. 2002 Aug;104(2):151-60. doi: 10.1006/clim.2002.5257.


Glutamine is the most abundant amino acid in the body. A decrease of plasma glutamine concentrations is found in catabolic stress and is related to susceptibility to infections. Glutamine is known to modulate lymphocyte activation; however, little is known about glutamine modulation of cell death of activated human T cells. Using Jurkat T cells, we investigated glutamine modulation of T-cell apoptosis activated by PMA plus ionomycin. We found that glutamine at various concentrations significantly enhanced IL-2 production, cell proliferation, and cell viability of Jurkat T cells. Glutamine also decreased the number of apoptotic cells stimulated with PMA plus ionomycin as demonstrated by flow cytometry. Meanwhile, glutamine down-regulated CD95 and CD95L expression, but up-regulated CD45RO and Bcl-2 expression in activated T cells. Further investigation of CD95-mediated caspase activities revealed that supplementation of glutamine significantly decreased caspase-3 and caspase-8 activities in activated T cells. Since oxidative stress is closely associated with induction of lymphocyte apoptosis, we found that glutamine significantly increased glutathione (GSH), but decreased reactive oxygen species levels in activated T cells. Blockade of intracellular GSH formation enhanced, but exogenous GSH supplementation decreased, activated T-cell apoptosis. Studying normal peripheral lymphoproliferation, we also found that the presence of glutamine increased lymphoproliferation as well as Bcl-2 and CD95 expression; but decreased CD95L and activation-induced T-cell death. Taken together, glutamine appeared to augment lymphoproliferation but suppressed activation-induced T-cell death in both Jurkat T cells and human peripheral T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Division
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein
  • Glutamine / pharmacology*
  • Glutathione / biosynthesis
  • Glutathione / metabolism*
  • Humans
  • Interleukin-2 / biosynthesis
  • Ionomycin / pharmacology
  • Jurkat Cells
  • Leukocyte Common Antigens / biosynthesis
  • Membrane Glycoproteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation
  • fas Receptor / biosynthesis


  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-2
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Glutamine
  • Ionomycin
  • Leukocyte Common Antigens
  • Glutathione
  • Tetradecanoylphorbol Acetate