Related Experiment Video
Updated: Aug 10, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
CD40 ligand inhibits Fas/CD95-mediated apoptosis of human blood-derived dendritic cells
T A Koppi1, T Tough-Bement, D M Lewinsohn
1Department of Microbiology, The University of Western Australia, Perth.
Insights
Dendritic cells (DCs) undergo apoptosis, regulated by Fas/CD95 signaling. CD40 ligand inhibits this cell death, impacting T cell responses during antigen presentation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are potent antigen-presenting cells (APCs) crucial for initiating immune responses.
- Understanding DC apoptosis regulation is vital for controlling immune duration and cytokine production.
Purpose of the Study:
- To investigate the regulation of apoptosis in human peripheral blood-derived dendritic cells.
- To identify key molecular pathways involved in DC cell death and survival.
Main Methods:
- Generation of dendritic cells from peripheral blood mononuclear cells using GM-CSF and IL-4.
- Analysis of DC phenotype, including dendritic processes and marker expression (CD1a, CD14).
- Assessment of apoptosis induction via Fas/CD95 stimulation and inhibition by CD40 ligand.
Main Results:
- Generated cells exhibited DC phenotype and potent antigen-presenting capacity.
- Fas/CD95 antigen expression on DCs mediated apoptotic cell death upon antibody stimulation.
- Soluble trimeric CD40 ligand effectively inhibited both CD95-mediated and spontaneous DC apoptosis.
Conclusions:
- Fas/CD95 signaling plays a significant role in DC apoptosis.
- CD40 ligand interaction modulates DC apoptosis, influencing T cell expansion and cytokine production.
- Tumor necrosis factor family ligand interactions regulate DC apoptosis during antigen presentation.
Abstract:
Dendritic cells (DC) are considered to be the most potent antigen-presenting cells (APC) in the immune system. In this study, we analyzed the regulation of apoptosis of human peripheral blood-derived DC. DC were generated from adherent peripheral blood mononuclear cells that had been cultured for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4. These cells displayed phenotypic properties of DC, including dendritic processes, expression of CD1a and lack of expression of CD14, and were very potent at presenting soluble antigens to T cells. Blood-derived DC were demonstrated to express the Fas/CD95 antigen and an agonist antibody to CD95 strongly induced apoptotic cell death in these cells. Soluble trimeric CD40 ligand potently inhibited both CD95-mediated and spontaneous apoptosis in DC. The data suggest that interactions between members of the tumor necrosis factor family of ligands expressed by T cells with their receptors on DC play an important role in the regulation of apoptosis in DC during antigen presentation and may, therefore, regulate the duration of T cell expansion and cytokine production.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:31The Intrinsic Apoptotic Pathway
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.