Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.
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Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production. / Würtzen, P A; Nissen, Mogens Holst; Claesson, M H.
In: Scandinavian Journal of Immunology, Vol. 53, No. 6, 2001, p. 579-87.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Maturation of dendritic cells by recombinant human CD40L-trimer leads to a homogeneous cell population with enhanced surface marker expression and increased cytokine production.
AU - Würtzen, P A
AU - Nissen, Mogens Holst
AU - Claesson, M H
N1 - Keywords: Antigen Presentation; Antigens, Differentiation, Myelomonocytic; CD40 Ligand; Cell Differentiation; Cells, Cultured; Cytokines; Dendritic Cells; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Monocytes; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Tuberculin; Tumor Necrosis Factor-alpha
PY - 2001
Y1 - 2001
N2 - Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.
AB - Dendritic cells (DC) have been shown to be potent inducers of specific cytotoxic T-cell responses both in vivo and in vitro. Furthermore, exposure to cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering changes DC phenotype and cytokine production and may enhance the T-cell activating capacity of the DC. We studied DC phenotype and cytokine production as well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activation induced by DC generated in vitro. In addition, the effect of exposure to recombinant human CD40L-trimer (huCD40LT) on these parameters was investigated. Effective differentiation of monocytes derived from freshly isolated peripheral blood mononuclear cells (PBMC) was obtained with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC expression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 was markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exposure. Only a moderate cytokine production was observed initially, while TNF-alpha addition or CD40 triggering, especially, induced enhanced production of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proliferation by a DC allostimulus or through the presentation of PPD, and influenza M1-peptide specific CTL activity was obtained with nonmaturated (CD83-) and maturated (CD83+) DC. In conclusion, a final maturation of monocyte-derived DC through huCD40LT resulted in a highly homogeneous cell population with enhanced surface marker expression and high production of pro-inflammatory cytokines. In addition, the induction of responses to allo or recall antigens presented by huCD40LT maturated DC was comparable to the responses obtained with the DC maturated through TNF-alpha exposure.
M3 - Journal article
C2 - 11422906
VL - 53
SP - 579
EP - 587
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
SN - 0301-6323
IS - 6
ER -
ID: 8746281