Functions of glutathione and glutathione disulfide in immunology and immunopathology

W Dröge, K Schulze‐Osthoff, S Mihm… - The FASEB …, 1994 - Wiley Online Library
W Dröge, K Schulze‐Osthoff, S Mihm, D Galter, H Schenk, HP Eck, S Roth, H Gmünder
The FASEB journal, 1994Wiley Online Library
Even a moderate increase in the cellular cysteine supply elevates the intracellular
glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological
functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the
immunologically important transcription factor NFxB, whereas high GSSG levels inhibit the
DNA binding activity of NFxB. The effects of GSSG are antagonized by reduced thioredoxin
(TRX). As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells …
Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the immunologically important transcription factor NFxB, whereas high GSSG levels inhibit the DNA binding activity of NFxB. The effects of GSSG are antagonized by reduced thioredoxin (TRX). As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide, they are likely targets for GSSG action. These redox‐regulated enzymes trigger signal cascades for NFxB activation and transduce signals from the T cell antigen receptor, from CD4 and CD8 molecules, and from the IL‐2 receptor β‐chain. The effector phase of cytotoxic T cell responses and IL‐2‐dependent functions are inhibited even by a partial depletion of the intracellular GSH pool. As signal transduction is facilitated by prooxidant conditions, we propose that the well‐known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency. As HIV‐infected patients and SIV‐infected rhesus macaques have, on the average, significantly decreased plasma cyst(e)ine and intracellular GSH levels, we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well.—Dröge, W., Schulze‐Osthoff, K., Mihm, S., Galter, D., Schenk, H., Eck, H.‐P., Roth, S., Gmünder, H. Functions of glutathione and glutathione disulfide in immunology and immunopathology. FASEB J. 8, 1131‐1138 (1994)
Wiley Online Library