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Expression and function of OX40 ligand on human dendritic cells
Y Ohshima1, Y Tanaka, H Tozawa
1University of Montreal, Centre de Recherche Louis-Charles Simard, Notre Dame Hospital, Quebec, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|October 23, 1997
Summary
OX40 ligand (OX40L) expressed on dendritic cells (DCs) enhances T cell priming. Ligation of OX40L on DCs boosts cytokine production and promotes DC maturation, suggesting a key role in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- OX40 ligand (OX40L) is a TNF family member that signals cells expressing it and its receptor, OX40.
- Dendritic cells (DCs) are potent antigen-presenting cells (APCs) crucial for naive T cell priming.
Purpose of the Study:
- To investigate the expression and functional role of OX40L on human dendritic cells (DCs).
- To determine how OX40L influences DC activation, maturation, and cytokine production during T cell priming.
Main Methods:
- Monocyte-derived DCs (Mo-DCs) and blood DCs (bDCs) were analyzed for OX40L expression.
- Monoclonal antibodies (mAbs) were used to stimulate or detect OX40L on DCs.
- Changes in DC cytokine production, surface molecule expression, and morphology were assessed after OX40L ligation.
Main Results:
- Both Mo-DCs and bDCs express OX40L, with expression modulated by differentiation and stimulation (e.g., CD40 ligation).
- OX40L ligation on activated IL-4-Mo-DCs significantly increased cytokine production (TNF-α, IL-12, IL-1β, IL-6) and co-stimulatory molecule expression (CD80, CD86, CD54, CD40).
- Stimulation via OX40L promoted DC maturation, indicated by CD83 upregulation and morphological changes.
Conclusions:
- OX40L expression on DCs plays a significant role in T cell priming.
- OX40L acts as a co-stimulatory molecule, enhancing both T cell activation and DC differentiation/maturation.