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Expression and function of OX40 ligand on human dendritic cells.

Y Ohshima, Y Tanaka, H Tozawa, Y Takahashi, C Maliszewski and G Delespesse
J Immunol October 15, 1997, 159 (8) 3838-3848;
Y Ohshima
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Y Tanaka
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H Tozawa
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Y Takahashi
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C Maliszewski
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G Delespesse
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Abstract

OX40 ligand (OX40L), a member of the TNF family, was shown to be capable of signaling both the cells on which it is expressed and those expressing OX40, its cognate receptor. Here we show that OX40L is expressed on dendritic cells (DC), the most efficient APC to prime naive T cells. The expression and the functional activity of OX40L were examined by means of mAbs used to stain or cross-link OX40L on 1) freshly isolated human blood DC (bDC) and 2) monocyte-derived DC at different stages of differentiation. These were derived from monocytes cultured either with IL-4 and granulocyte-macrophage CSF (IL-4-Mo-DC) or with IL-4 and granulocyte-macrophage CSF plus TNF-alpha. Both types of Mo-DC expressed OX40L after stimulation through CD40; ligation of OX40L on activated IL-4-Mo-DC enhanced by 4- to 35-fold their cytokine production (TNF-alpha, IL-12 p40, IL-1 beta, and IL-6) and increased CD80, CD86, CD54, and CD40 expression. Stimulation of activated IL-4-Mo-DC through OX40L strikingly enhanced their maturation as evidenced by CD83 up-regulation, CD115 (CSF-1R) down-regulation, and typical morphologic changes. OX40L was constitutively expressed on a subset of bDC, and its ligation slightly enhanced CD40L-stimulated IL-12 production. OX40L was down-regulated after overnight culture and spontaneously reexpressed on a subset of mature bDC (CD83high, CD33high, CD11chigh, CD5+). Thus, the expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation.

  • Copyright © 1997 by American Association of Immunologists
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The Journal of Immunology
Vol. 159, Issue 8
15 Oct 1997
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Expression and function of OX40 ligand on human dendritic cells.
Y Ohshima, Y Tanaka, H Tozawa, Y Takahashi, C Maliszewski, G Delespesse
The Journal of Immunology October 15, 1997, 159 (8) 3838-3848;

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Expression and function of OX40 ligand on human dendritic cells.
Y Ohshima, Y Tanaka, H Tozawa, Y Takahashi, C Maliszewski, G Delespesse
The Journal of Immunology October 15, 1997, 159 (8) 3838-3848;
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Print ISSN 0022-1767        Online ISSN 1550-6606