gamma-Glutamyl transpeptidase is up-regulated on memory T lymphocytes

The ectoenzyme gamma-glutamyl transpeptidase (GGT) hydrolyzes glutathione ( GSH), is required for the maintenance of normal intracellular GSH levels an d modifies the activity of GSH-containing adducts, Previous data suggested that this enzyme was present on mitogen-activated T lymphocytes, However, t he level of GGT protein expression on human mononuclear cell subsets has no t been determined, A novel mAb to human GGT, 3A8, was developed. 3A8 was us ed to show that the expression of GGT is, in fact, highest on resting T cel ls that express markers of the memory phenotype, specifically CD45RO and de creased expression of CD45RB, The peripheral blood of patients with rheumat oid arthritis was found to have expanded numbers of T cells expressing leve ls of GGT up to 10-fold higher than controls. In addition, the CD4(+) T cel l subset with the capacity to migrate across a human endothelial cell monol ayer expresses high GGT levels. GGT expression was up-regulated on peripher al blood T cells following activation in vitro by either superantigen, phor bol ester, or IL-15, a stimulatory cytokine synthesized in rheumatoid synov ium. Resting peripheral blood T cells that express GGT have higher levels o f intracellular thiols than those that do not. These observations suggest t hat GGT may play an important role in the regulation of lymphocytes that ar e at a particular developmental stage.