Related Experiment Videos
Induction of TRAIL-mediated glioma cell death by human T cells
Jan Dörr1, Sonia Waiczies, Uwe Wendling
1Division of Neuroimmunology, Department of Neurology, Charité, Neuroscientific Research Center, 10098, Berlin, Germany.
Abstract:
Among the death ligands of the tumor necrosis factor/nerve growth factor (TNF/NGF) superfamily, TNF-related apoptosis-inducing ligand (TRAIL) is considered to play a unique role due to its binding to both apoptosis-inducing and -blocking membranous receptors, apoptosis-independent effects and distinct species differences. Here, we demonstrate that human antigen-specific T helper cells upon activation are capable of directly lysing glioma cell lines via TRAIL receptor/TRAIL interactions. Out of 17 T cell lines, nine showed predominantly TRAIL-mediated killing of glioma cell lines compared to CD95 ligand- or TNF-induced cell death. The cytotoxic potential of the T cell lines was independent of T helper differentiation, antigen specificity and donor source. Thus, TRAIL-mediated signaling is involved in T cell cytotoxicity towards glioma cell lines, which might play an important role in tumor regression.
Insights
Activated T helper cells can kill glioma cells using TNF-related apoptosis-inducing ligand (TRAIL) signaling. This TRAIL-mediated cytotoxicity against glioma cell lines may contribute to tumor regression.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Tumor Necrosis Factor (TNF)/Nerve Growth Factor (NGF) superfamily includes death ligands with diverse roles.
- TNF-related apoptosis-inducing ligand (TRAIL) has unique properties, including dual receptor binding and species-specific effects.
- The role of TRAIL in T cell-mediated cytotoxicity against cancer, particularly glioma, requires further elucidation.
Purpose of the Study:
- To investigate whether activated human antigen-specific T helper cells can directly lyse glioma cell lines.
- To determine the role of TRAIL receptor/TRAIL interactions in T cell-mediated glioma cell killing.
- To compare TRAIL-mediated killing with other cytotoxic pathways like CD95 ligand and TNF.
Main Methods:
- Co-culture of activated human antigen-specific T helper cell lines with glioma cell lines.
- Assessment of glioma cell lysis using TRAIL receptor/TRAIL interactions.
- Comparison of cytotoxicity mediated by TRAIL, CD95 ligand, and TNF.
Main Results:
- Activated T helper cells demonstrated direct lysis of glioma cell lines.
- Nine out of 17 T cell lines predominantly used TRAIL-mediated killing.
- TRAIL-mediated cytotoxicity was independent of T helper differentiation, antigen specificity, and donor source.
Conclusions:
- TRAIL-mediated signaling is a significant mechanism in T cell cytotoxicity towards glioma cell lines.
- This TRAIL-driven immune response may play a crucial role in glioma tumor regression.
- Findings highlight TRAIL's potential as a therapeutic target in glioma treatment.