Inhibition of human dendritic cell functions by methylprednisolone

N Vanderheyde, V. Verhasselt, M Goldman, F Willems

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Background, The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC, Here, we analyzed how methylprednisolone (RIP) might affect the function and maturation of human DC,

Methods. Human DC were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L), DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity.

Results. Although MP did not affect viability of DC, it enhanced their antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. in contrast, when DC were stimulated by 3T6-CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC were deficient in their ability to elicit proliferative responses of CD4(+)CD45RA(+) allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13.

Conclusion. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.

Original languageEnglish
Pages (from-to)1342-1347
Number of pages6
JournalTransplantation
Volume67
Issue number10
DOIs
Publication statusPublished - 27 May 1999

Cite this

Vanderheyde, N ; Verhasselt, V. ; Goldman, M ; Willems, F. / Inhibition of human dendritic cell functions by methylprednisolone. In: Transplantation. 1999 ; Vol. 67, No. 10. pp. 1342-1347.
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abstract = "Background, The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC, Here, we analyzed how methylprednisolone (RIP) might affect the function and maturation of human DC,Methods. Human DC were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L), DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity.Results. Although MP did not affect viability of DC, it enhanced their antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. in contrast, when DC were stimulated by 3T6-CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC were deficient in their ability to elicit proliferative responses of CD4(+)CD45RA(+) allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13.Conclusion. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.",
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Inhibition of human dendritic cell functions by methylprednisolone. / Vanderheyde, N; Verhasselt, V.; Goldman, M; Willems, F.

In: Transplantation, Vol. 67, No. 10, 27.05.1999, p. 1342-1347.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of human dendritic cell functions by methylprednisolone

AU - Vanderheyde, N

AU - Verhasselt, V.

AU - Goldman, M

AU - Willems, F

PY - 1999/5/27

Y1 - 1999/5/27

N2 - Background, The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC, Here, we analyzed how methylprednisolone (RIP) might affect the function and maturation of human DC,Methods. Human DC were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L), DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity.Results. Although MP did not affect viability of DC, it enhanced their antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. in contrast, when DC were stimulated by 3T6-CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC were deficient in their ability to elicit proliferative responses of CD4(+)CD45RA(+) allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13.Conclusion. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.

AB - Background, The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC, Here, we analyzed how methylprednisolone (RIP) might affect the function and maturation of human DC,Methods. Human DC were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4. DC maturation was induced either by lipopolysaccharide (LPS) or by fibroblast transfected with the CD40-ligand gene (3T6-CD40L), DC phenotype was characterized by flow cytometric analysis, their cytokine production by ELISA. The ability of DC to activate naive T cells was evaluated in mixed leukocyte reactivity.Results. Although MP did not affect viability of DC, it enhanced their antigen uptake and down-regulated their basal expression of CD86. The expression of CD80 and CD54 by DC was slightly decreased and HLA-DR expression was not modified. MP prevented LPS-induced DC maturation as assessed by the inhibition of CD86, CD80 and CD54 up-regulation, CD83 induction and production of TNF-alpha, IL-6, and IL-12. in contrast, when DC were stimulated by 3T6-CD40L, MP prevented only the synthesis of IL-12. Moreover, MP-treated DC were deficient in their ability to elicit proliferative responses of CD4(+)CD45RA(+) allogeneic T cells as well as their synthesis of interferon (IFN)-gamma, IL-5, and IL-13.Conclusion. Glucocorticoids exert potent suppressive effects on human DC and thereby inhibit the induction of primary T cell responses.

KW - COLONY-STIMULATING FACTOR

KW - T-CELLS

KW - NUCLEAR-LOCALIZATION

KW - CD4(+) LYMPHOCYTES

KW - IL-12 PRODUCTION

KW - HUMAN BLOOD

KW - IN-VIVO

KW - GLUCOCORTICOIDS

KW - EXPRESSION

KW - CD40

U2 - 10.1097/00007890-199905270-00009

DO - 10.1097/00007890-199905270-00009

M3 - Article

VL - 67

SP - 1342

EP - 1347

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 10

ER -