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B Inhibition1
*
Laboratory of Experimental Immunology and Centre de Recherche Interuniversitaire en Vaccinologie, Université Libre de Bruxelles, Brussels, Belgium; and
Department of Molecular Biology and Flanders Interuniversity Institute for Biotechnology, University of Gent, Belgium
N-acetyl-L-cysteine (NAC) is an
antioxidant molecule endowed with immunomodulatory 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 CSF.
We first found that NAC inhibited the constitutive as well as the
LPS-induced activity of the transcription factor NF-
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 basal state and upon LPS activation. NAC also
inhibited DC responses induced by CD40 engagement. The inhibitory
effects of NAC were not due to nonspecific toxicity as neither the
viability of DC nor their mannose receptor-mediated endocytosis were
modified by NAC. Finally, we found that the addition of NAC to MLR
between naive T cells and allogeneic DC resulted in a profound
inhibition of alloreactive responses, which could be attributed to a
defect of DC as APC-independent T cell responses were not inhibited by
NAC. Altogether, our results suggest that NAC might impair the
generation of primary immune responses in humans through its inhibitory
action on DC.
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