TY - JOUR
T1 - γ-glutamyl transpeptidase is up-regulated on memory T lymphocytes
AU - Karp, David R.
AU - Carlisle, Margaret L.
AU - Mobley, Angela B.
AU - Nichols, Timothy C.
AU - Oppenheimer-Marks, Nancy
AU - Brezinschek, Ruth I.
AU - Holers, V. Michael
PY - 1999
Y1 - 1999
N2 - The ectoenzyme γ-glutamyl transpeptidase (GGT) hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH levels and modifies the activity of GSH-containing adducts. Previous data suggested that this enzyme was present on mitogen-activated T lymphocytes. However, the level of GGT protein expression on human mononuclear cell subsets has not been determined. A novel mAb to human GGT, 3A8, was developed. 3A8 was used to show that the expression of GGT is, in fact, highest on resting T cells that express markers of the memory phenotype, specifically CD45RO and decreased expression of CD45RB. The peripheral blood of patients with rheumatoid arthritis was found to have expanded numbers of T cells expressing levels of GGT up to 10-fold higher than controls. In addition, the CD4+ T cell subset with the capacity to migrate across a human endothelial cell monolayer expresses high GGT levels. GGT expression was up-regulated on peripheral blood T cells following activation in vitro by either superantigen, phorbol ester, or IL-15, a stimulatory cytokine synthesized in rheumatoid synovium. Resting peripheral blood T cells that express GGT have higher levels of intracellular thiols than those that do not. These observations suggest that GGT may play an important role in the regulation of lymphocytes that are at a particular developmental stage.
AB - The ectoenzyme γ-glutamyl transpeptidase (GGT) hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH levels and modifies the activity of GSH-containing adducts. Previous data suggested that this enzyme was present on mitogen-activated T lymphocytes. However, the level of GGT protein expression on human mononuclear cell subsets has not been determined. A novel mAb to human GGT, 3A8, was developed. 3A8 was used to show that the expression of GGT is, in fact, highest on resting T cells that express markers of the memory phenotype, specifically CD45RO and decreased expression of CD45RB. The peripheral blood of patients with rheumatoid arthritis was found to have expanded numbers of T cells expressing levels of GGT up to 10-fold higher than controls. In addition, the CD4+ T cell subset with the capacity to migrate across a human endothelial cell monolayer expresses high GGT levels. GGT expression was up-regulated on peripheral blood T cells following activation in vitro by either superantigen, phorbol ester, or IL-15, a stimulatory cytokine synthesized in rheumatoid synovium. Resting peripheral blood T cells that express GGT have higher levels of intracellular thiols than those that do not. These observations suggest that GGT may play an important role in the regulation of lymphocytes that are at a particular developmental stage.
KW - Cell surface molecules
KW - Cellular differentiation
KW - Glutathione
KW - Human
KW - Rheumatoid arthritis
KW - T lymphocytes
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U2 - 10.1093/intimm/11.11.1791
DO - 10.1093/intimm/11.11.1791
M3 - Article
C2 - 10545483
AN - SCOPUS:0032738764
SN - 0953-8178
VL - 11
SP - 1791
EP - 1800
JO - International Immunology
JF - International Immunology
IS - 11
ER -