cAMP-mediated suppression of a Th1 clone associated with an alteration of the intracellular redox environment

2003 
We have shown previously that the elevation of intracellular cAMP in antigen or anti-CD3-activated murine Th I clones in the absence of antigen inhibits antigen-induced proliferation and the production of IL-2 by H 2 O 2 -mediated oxidation of p56 l c k and inhibits antigen-induced production of interferon-y by the induction of intracellular nitric oxide. Moreover, activated Th1 clones are resistant to cAMP-induced suppression. These results suggest that the immunosuppression of Thl cells mediated by elevated intracellular cAMP is associated with an alteration in the intracellular oxidation/reduction environment. Here we report that the culture of an antigen or anti-CD3-activated murine Th I clone with the adenylcyclase agonist forskolin (FSK) in the absence of antigen reduces the activity of intracellular catalase, and diminishes levels of intracellular reduced glutathione (GSH). Resting cells resistant to cAMP-induced suppression have higher intracellular GSH levels than antigen-activated cells susceptible to cAMP-induced suppression. The results provide further evidence that cAMP-induced suppression of Th1 clones is mediated by profound alterations in the intracellular redox environment and may be used to selectively inactivate Th1 cells activated by antigen.
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