Journal article
The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion
The Journal of immunology (1950), Vol.175(12), pp.7965-7972
12/15/2005
DOI: 10.4049/jimmunol.175.12.7965
PMID: 16339532
Abstract
Glutathione (GSH) is an abundant intracellular tripeptide that has been implicated as an important regulator of T cell proliferation. The effect of pharmacological regulators of GSH and other thiols on murine T cell signaling, proliferation, and intracellular thiol levels was examined. l-Buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH synthesis, markedly reduced GSH levels and blocked T cell proliferation without significant effect on cell viability. N-acetylcysteine markedly enhanced T cell proliferation without affecting GSH levels. Cotreatment of T cells with N-acetylcysteine and BSO failed to restore GSH levels, but completely restored the proliferative response. Both 2-ME and l-cysteine also reversed the BSO inhibition of T cell proliferation. Intracellular l-cysteine levels were reduced with BSO treatment and restored with cotreatment with NAC or l-cysteine. However, 2-ME completely reversed the BSO inhibition of proliferation without increasing intracellular cysteine levels. Therefore, neither GSH nor cysteine is singularly critical in limiting T cell proliferation. Reducing equivalents from free thiols were required because oxidation of the thiol moiety completely abolished the effect. Furthermore, BSO did not change the expression of surface activation markers, but effectively blocked IL-2 and IL-6 secretion. Importantly, exogenous IL-2 completely overcame BSO-induced block of T cell proliferation. These results demonstrate that T cell proliferation is regulated by thiol-sensitive pathway involving IL-2.
Details
- Title: Subtitle
- The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion
- Creators
- Tanja Hadzic - Department of Pathology, University of Iowa, Iowa City, 52242, USALing LiNingli ChengSusan A WalshDouglas R SpitzC Michael Knudson
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.175(12), pp.7965-7972
- Publisher
- United States
- DOI
- 10.4049/jimmunol.175.12.7965
- PMID
- 16339532
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- P01CA066081 / NCI NIH HHS R01CA88967 / NCI NIH HHS R01CA100045 / NCI NIH HHS
- Language
- English
- Date published
- 12/15/2005
- Academic Unit
- Radiology; Pathology; Radiation Oncology
- Record Identifier
- 9984046903702771
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