Background
Superantigens produced by group A streptococci (GAS) and Staphylococcus aureus are key mediators of toxic shock syndrome (TSS) through their potent activation of T cells. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are activated in the acute phase of streptococcal TSS (STSS), and main producers of inflammatory cytokines in response to superantigens. After activation the MAIT cell frequency decreases. Targeting MAIT cell activation could therefore be a therapeutic strategy in these patients. N-acetylcysteine (NAC) is an antioxidant with anti-inflammatory and anti-apoptotic properties which serves as a substrate for glutathione (GSH) synthesis. Here we aimed to test if NAC and GSH can inhibit the cytokine production in MAIT cells treated with GAS and S. aureus.
Methods
Freshly isolated PBMC from healthy blood donors were treated with supernatants from GAS and S. aureus in the presence of NAC or GSH. MAIT cell activation and cytokine production were assessed by multiparameter flow cytometry.
Results
NAC reduced IFNg and TNF production by 50-70% in MAIT cells stimulated with GAS, and 60-90% in MAIT cells stimulated with S. aureus. Cytokine production in other CD45RO+ T cells was unaffected. Similar results were obtained with GSH. NAC and GSH also caused a decrease in CD69 expression in all T cell subsets analyzed. NAC treatment prevented the loss of MAIT cells after stimulation and reduced the expression of activated caspase-3.
Conclusions
The antioxidants NAC and GSH have the potential to block superantigen-triggered inflammatory cytokine production in MAIT cells.