N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level: Association with NF-kappa B inhibition

N-acetyl-L-cysteine (NAC) is an antioxidant molecule endowed with immunomod ulatory properties. To investigate the effect of NAC on the induction phase of T cell responses, we analyzed its action on human dendritic cells (DC) derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CS F, We first found that NAC inhibited the constitutive as well as the LPS-in duced activity of the transcription factor NF-kappa B. In parallel, NAC was shown to down-regulate the production of cytokines by DC as well as their surface expression of HLA-DR, CD86 (B7-2), and CD40 molecules both at the b asal state and upon LPS activation. NAC also inhibited DC responses induced by CD40 engagement. The inhibitory effects of NAC were not due to nonspeci fic toxicity as neither the viability of DC nor their mannose receptor-medi ated endocytosis were modified by NAG. Finally, we found that the addition of NAC to MLR between naive T cells and allogeneic DC resulted in a profoun d inhibition of alloreactive responses, which could be attributed to a defe ct of DC as APC-independent T cell responses were not inhibited by NAC. Alt ogether, our results suggest that NAC might impair the generation of primar y immune responses in humans through its inhibitory action on DC.