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

Valérie Verhasselt, Wim Vanden Berghe, Nathalie Vanderheyde, Fabienne Willems, Guy Haegeman, Michel Goldman

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

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-κB. 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.

Original languageEnglish
Pages (from-to)2569-2574
Number of pages6
JournalJournal of Immunology
Volume162
Issue number5
Publication statusPublished - 1 Mar 1999
Externally publishedYes

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Acetylcysteine
Dendritic Cells
T-Lymphocytes
HLA-DR Antigens
Endocytosis
Granulocytes
Interleukin-4
Transcription Factors
Down-Regulation
Antioxidants
Macrophages
Cytokines

Cite this

Verhasselt, V., Vanden Berghe, W., Vanderheyde, N., Willems, F., Haegeman, G., & Goldman, M. (1999). N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level: Association with NF-κB inhibition. Journal of Immunology, 162(5), 2569-2574.
Verhasselt, Valérie ; Vanden Berghe, Wim ; Vanderheyde, Nathalie ; Willems, Fabienne ; Haegeman, Guy ; Goldman, Michel. / N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level : Association with NF-κB inhibition. In: Journal of Immunology. 1999 ; Vol. 162, No. 5. pp. 2569-2574.
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Verhasselt, V, Vanden Berghe, W, Vanderheyde, N, Willems, F, Haegeman, G & Goldman, M 1999, 'N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level: Association with NF-κB inhibition' Journal of Immunology, vol. 162, no. 5, pp. 2569-2574.

N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level : Association with NF-κB inhibition. / Verhasselt, Valérie; Vanden Berghe, Wim; Vanderheyde, Nathalie; Willems, Fabienne; Haegeman, Guy; Goldman, Michel.

In: Journal of Immunology, Vol. 162, No. 5, 01.03.1999, p. 2569-2574.

Research output: Contribution to journalArticle

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T1 - N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level

T2 - Association with NF-κB inhibition

AU - Verhasselt, Valérie

AU - Vanden Berghe, Wim

AU - Vanderheyde, Nathalie

AU - Willems, Fabienne

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AU - Goldman, Michel

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AB - 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-κB. 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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