Apoptotic contraction drives target cell release by cytotoxic T cells
Elisa E Sanchez1, Maria Tello-Lafoz1, Aixuan J Guo1
1Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature Immunology
|July 27, 2023
Summary
Cytotoxic T lymphocytes (CTLs) detach from target cells when the targets undergo cytoskeletal contraction. This contraction is key for immune synapse dissolution and enables CTLs to kill more cells.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- Cytotoxic T lymphocytes (CTLs) are crucial for eliminating infected or cancerous cells.
- CTLs form immune synapses (IS) to deliver cytotoxic molecules, leading to target cell death.
- The mechanisms of IS dissolution and CTL detachment are less understood than IS assembly.
Purpose of the Study:
- To investigate the biophysical mechanisms underlying immune synapse dissolution.
- To determine the role of target cell contractility in CTL detachment.
Main Methods:
- Time-lapse imaging of CTL-target cell interactions.
- Genetic and pharmacological manipulation of target cell cytoskeletal contraction.
- Analysis of immune synapse dynamics and CTL serial killing capacity.
Main Results:
- Immune synapse dissolution correlates with apoptotic target cell cytoskeletal contraction.
- Target cell contraction is necessary and sufficient for CTL dissociation.
- Enhanced apoptotic contractility accelerates CTL detachment and serial killing.
Conclusions:
- Target cell cytoskeletal contraction provides a biophysical basis for immune synapse dissolution.
- Mechanosensory feedback during apoptosis regulates CTL-target cell interactions.
- Understanding IS dissolution is vital for optimizing T cell-based therapies.
More Related Videos
Related Concept Videos
01:27Cytotoxic T Cells-mediated Immune Response
974
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
974
01:17The Extrinsic Apoptotic Pathway
6.5K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.5K
01:18Autophagic Cell Death
3.5K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.5K
01:30Apoptosis
11.6K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.6K
01:17Phagocytosis of Apoptotic Cells
3.9K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
3.9K
01:31The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K