γ-Glutamyl transpeptidase activity alters the T cell response to oxidative stress and Fas-induced apoptosis

Margaret L. Carlisle, Miranda R. King, David R. Karp

Research output: Contribution to journalReview article

21 Scopus citations

Abstract

The ectoenzyme γ-glutamyl transpeptidase (GGT) is absent on resting naive peripheral blood T cells, highly expressed upon stimulation and intermediate on resting memory T cells. In other tissues, GGT is essential for the recapture of the antioxidant glutathione (GSH). T cells with different levels of GGT activity were examined for their ability to withstand oxidative stress. To create a model system that reflected the level of GGT seen on naive and memory T cells, Jurkat T cells were cloned by limiting dilution and their GGT expression analyzed. Jurkat expressing GGT at levels comparable to resting memory T cells have levels of intracellular reactive oxygen species (ROS) that are only 65% that seen in Jurkat that have low levels of GGT (similar to naive T cells). Treatment of the cells with H2O2 increases ROS in both cells, although the level seen in the GGThigh Jurkat is less than half that in the GGTlow variant. Despite protection from oxidative stress, the GGThigh Jurkat were found to be 2- to 3-fold more sensitive to Fas-induced apoptosis. The redox-regulated NF-κB pathway is activated in GGTlow cells, resulting in higher levels of cIAP-1/2 proteins that limit caspase activity. The GGTlow cells were found to have higher levels of NF-κB in the nucleus as well as lower levels of IκB-α. The GGTlow cells also express higher levels of the caspase inhibitors cIAP-1/2 and have lower levels of caspase activity. These findings suggest that GGT expression regulates ROS in T lymphocytes and modulates Fas-induced killing by altering NF-κB activity.

Original languageEnglish (US)
Pages (from-to)17-27
Number of pages11
JournalInternational Immunology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Apoptosis
  • Human
  • T lymhocyte
  • Transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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