Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells

The thiol antioxidant N-acetyl-L-cysteine (NAC), known as a precursor of gl utathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH a nd NAC are known to enhance T cell proliferation, production of IL-2 and up -regulation of the IL-2 receptor. The 120-kD CD30 surface antigen belongs t o the tumour necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper (Th) cells and its expression is sustained in Th2 cells . We have analysed the effect of GSH and NAC on the cytokine profile and CD 30 expression on human allergen-specific T cell clones (TCC). TCC were stim ulated with anti-CD3 antibodies in the presence of different concentrations of GSH and NAC. Both thiols caused a dose dependent down-regulation of IL- 4, IL-5 and IFN-gamma levels in Th0 and Th2 clones, with the most pronounce d decrease of IL-4. Furthermore, they down-regulated the surface expression of CD30, and the levels of soluble CD30 (sCD30) in the culture supernatant s were decreased. In contrast, the surface expression of CD28 or CD40 ligan d (CD40L) was not significantly changed after treatment with 20 m m NAC. Th ese results indicate that GSH and NAC favour a Th1 response by a preferenti al down-regulation of IL-4. In addition, the expression of CD30 was down re gulated by GSH and NAC, suggesting that CD30 expression is dependent on IL- 4, or modified by NAC. In the likely event that CD30 and its soluble counte rpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the trea tment of these diseases.