期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：9
页码：3343-3347
DOI：10.1073/pnas.87.9.3343
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Regulation of proliferation of normal human T lymphocytes (T cells) by glutathione (GSH) was explored with T-cell activation models that do not require accessory cell signals. L-Buthionine-(S,R)-sulfoximine (BSO), which inactivates gamma-glutamylcysteine synthetase and therefore inhibits GSH synthesis, inhibited proliferation elicited by monoclonal antibodies directed at cluster designation 2 (CD2) and CD3 antigens, or by sn-1,2-dioctanoylglycerol and ionomycin. L-Buthionine-(R)-sulfoximine, which does not inactivate gamma-glutamylcysteine synthetase, did not affect proliferation. BSO-induced inhibition of accessory cell-independent T-cell proliferation was not reversed by recombinant human interleukin 2, despite activation-dependent expression of interleukin 2 receptor alpha by T cells treated with BSO. However, BSO-associated inhibition of T-cell proliferation was reversed by GSH or GSH ester. These studies, which show that GSH can directly modulate proliferation of highly purified T cells, suggest that GSH is essential for steps close to or at DNA synthesis. The availability of methods for decreasing and for increasing GSH levels suggest therapies to produce (i) immunosuppression (of value in organ transplantation), and (ii) immunopotentiation (of potential value in treatment of immunodeficiency states such as AIDS).
