Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory T cells

O Vosters, J Neve, F Willems, M Goldman, V. Verhasselt, D. De Wit

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background. Drugs blocking dendritic cell (DC) maturation might be useful in transplantation by inhibiting the induction of primary alloimmune responses and promoting the emergence of regulatory T lymphocytes (Treg). We investigated the effects of Nacystelyn (NAL), an N-acetyl-L-cysteine derivative, on human DCs, paying attention to the T-cell responses elicited by NAL-treated DCs in vitro.

Methods. Lipopolysaccharide (LPS) was used to induce the maturation of DCs naturally present in blood or generated from human monocytes cultured in interleukin-4 and granulocyte-macrophage colony-stimulating activity. We first analyzed the consequences of NAL on cytokine production and expression of major histocompatibility complex class II and costimulatory molecules. Monocyte-derived DCs were then used as stimulators in mixed leukocyte cultures with naive CD4(+) T cells. Cytokine levels were measured in culture supernatants; the phenotype of T cells and their capacity to inhibit the proliferation of third-party T-cell responders was determined at the end of the culture.

Results. NAL proved to be a potent inhibitor of DC maturation in whole blood experiments and on monocyte-derived DCs. Alloreactive T cells stimulated with DCs pretreated with LPS in the presence of NAL produced much less interferon-gamma but similar levels of interleukin-13 compared with DCs treated with LPS alone. Immature DCs induced Treg, which was not observed with mature DCs. DCs cultured with LPS in the presence of NAL were as efficient as immature DCs to generate alloreactive T cells with regulatory activity.

Conclusions. NAL is a potent inhibitor of DC maturation, which might be useful to promote allograft acceptance by inducing the differentiation of allospecific Treg.

Original languageEnglish
Pages (from-to)383-389
Number of pages7
JournalTransplantation
Volume75
Issue number3
DOIs
Publication statusPublished - 15 Feb 2003

Cite this

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title = "Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory T cells",
abstract = "Background. Drugs blocking dendritic cell (DC) maturation might be useful in transplantation by inhibiting the induction of primary alloimmune responses and promoting the emergence of regulatory T lymphocytes (Treg). We investigated the effects of Nacystelyn (NAL), an N-acetyl-L-cysteine derivative, on human DCs, paying attention to the T-cell responses elicited by NAL-treated DCs in vitro.Methods. Lipopolysaccharide (LPS) was used to induce the maturation of DCs naturally present in blood or generated from human monocytes cultured in interleukin-4 and granulocyte-macrophage colony-stimulating activity. We first analyzed the consequences of NAL on cytokine production and expression of major histocompatibility complex class II and costimulatory molecules. Monocyte-derived DCs were then used as stimulators in mixed leukocyte cultures with naive CD4(+) T cells. Cytokine levels were measured in culture supernatants; the phenotype of T cells and their capacity to inhibit the proliferation of third-party T-cell responders was determined at the end of the culture.Results. NAL proved to be a potent inhibitor of DC maturation in whole blood experiments and on monocyte-derived DCs. Alloreactive T cells stimulated with DCs pretreated with LPS in the presence of NAL produced much less interferon-gamma but similar levels of interleukin-13 compared with DCs treated with LPS alone. Immature DCs induced Treg, which was not observed with mature DCs. DCs cultured with LPS in the presence of NAL were as efficient as immature DCs to generate alloreactive T cells with regulatory activity.Conclusions. NAL is a potent inhibitor of DC maturation, which might be useful to promote allograft acceptance by inducing the differentiation of allospecific Treg.",
keywords = "LYMPHOCYTE-ASSOCIATED ANTIGEN-4, IN-VIVO, N-ACETYLCYSTEINE, INHIBITION, TOLERANCE, RESPONSES, INTERLEUKIN-13, STIMULATION, IMMUNITY, SIGNALS",
author = "O Vosters and J Neve and F Willems and M Goldman and V. Verhasselt and {De Wit}, D.",
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Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory T cells. / Vosters, O; Neve, J; Willems, F; Goldman, M; Verhasselt, V.; De Wit, D.

In: Transplantation, Vol. 75, No. 3, 15.02.2003, p. 383-389.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory T cells

AU - Vosters, O

AU - Neve, J

AU - Willems, F

AU - Goldman, M

AU - Verhasselt, V.

AU - De Wit, D.

PY - 2003/2/15

Y1 - 2003/2/15

N2 - Background. Drugs blocking dendritic cell (DC) maturation might be useful in transplantation by inhibiting the induction of primary alloimmune responses and promoting the emergence of regulatory T lymphocytes (Treg). We investigated the effects of Nacystelyn (NAL), an N-acetyl-L-cysteine derivative, on human DCs, paying attention to the T-cell responses elicited by NAL-treated DCs in vitro.Methods. Lipopolysaccharide (LPS) was used to induce the maturation of DCs naturally present in blood or generated from human monocytes cultured in interleukin-4 and granulocyte-macrophage colony-stimulating activity. We first analyzed the consequences of NAL on cytokine production and expression of major histocompatibility complex class II and costimulatory molecules. Monocyte-derived DCs were then used as stimulators in mixed leukocyte cultures with naive CD4(+) T cells. Cytokine levels were measured in culture supernatants; the phenotype of T cells and their capacity to inhibit the proliferation of third-party T-cell responders was determined at the end of the culture.Results. NAL proved to be a potent inhibitor of DC maturation in whole blood experiments and on monocyte-derived DCs. Alloreactive T cells stimulated with DCs pretreated with LPS in the presence of NAL produced much less interferon-gamma but similar levels of interleukin-13 compared with DCs treated with LPS alone. Immature DCs induced Treg, which was not observed with mature DCs. DCs cultured with LPS in the presence of NAL were as efficient as immature DCs to generate alloreactive T cells with regulatory activity.Conclusions. NAL is a potent inhibitor of DC maturation, which might be useful to promote allograft acceptance by inducing the differentiation of allospecific Treg.

AB - Background. Drugs blocking dendritic cell (DC) maturation might be useful in transplantation by inhibiting the induction of primary alloimmune responses and promoting the emergence of regulatory T lymphocytes (Treg). We investigated the effects of Nacystelyn (NAL), an N-acetyl-L-cysteine derivative, on human DCs, paying attention to the T-cell responses elicited by NAL-treated DCs in vitro.Methods. Lipopolysaccharide (LPS) was used to induce the maturation of DCs naturally present in blood or generated from human monocytes cultured in interleukin-4 and granulocyte-macrophage colony-stimulating activity. We first analyzed the consequences of NAL on cytokine production and expression of major histocompatibility complex class II and costimulatory molecules. Monocyte-derived DCs were then used as stimulators in mixed leukocyte cultures with naive CD4(+) T cells. Cytokine levels were measured in culture supernatants; the phenotype of T cells and their capacity to inhibit the proliferation of third-party T-cell responders was determined at the end of the culture.Results. NAL proved to be a potent inhibitor of DC maturation in whole blood experiments and on monocyte-derived DCs. Alloreactive T cells stimulated with DCs pretreated with LPS in the presence of NAL produced much less interferon-gamma but similar levels of interleukin-13 compared with DCs treated with LPS alone. Immature DCs induced Treg, which was not observed with mature DCs. DCs cultured with LPS in the presence of NAL were as efficient as immature DCs to generate alloreactive T cells with regulatory activity.Conclusions. NAL is a potent inhibitor of DC maturation, which might be useful to promote allograft acceptance by inducing the differentiation of allospecific Treg.

KW - LYMPHOCYTE-ASSOCIATED ANTIGEN-4

KW - IN-VIVO

KW - N-ACETYLCYSTEINE

KW - INHIBITION

KW - TOLERANCE

KW - RESPONSES

KW - INTERLEUKIN-13

KW - STIMULATION

KW - IMMUNITY

KW - SIGNALS

U2 - 10.1097/01.TP.0000043924.09647.61

DO - 10.1097/01.TP.0000043924.09647.61

M3 - Article

VL - 75

SP - 383

EP - 389

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 3

ER -