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A new model for lethal hit delivery by cytotoxic T lymphocytes
P J Peters1, H J Geuze, H A van der Donk
1Laboratory of Cell Biology, Medical School, University of Utrecht, The Netherlands.
Immunology Today
|January 1, 1990
Summary
Cytotoxic T lymphocyte (CTL) granules release cytotoxic mediators within membrane-enveloped structures, not soluble forms. This membrane-enclosed delivery ensures targeted cell killing via molecules like perforin and serine esterases.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human cytotoxic T lymphocyte (CTL) granules are key effectors in cell-mediated immunity.
- These granules contain cytotoxic molecules essential for targeting and eliminating infected or cancerous cells.
Purpose of the Study:
- To revise the current model of cytotoxic T lymphocyte-mediated cell killing.
- To investigate the form and delivery mechanism of cytotoxic mediators during CTL-target cell interactions.
Main Methods:
- Immuno-electron microscopy was employed to visualize the ultrastructure of CTL granules.
- Localization of key molecules, including perforin and serine esterases, within granule substructures was determined.
Main Results:
- CTL granules possess an electron-dense core and associated membrane vesicles.
- Molecules crucial for CTL-target cell (TC) interaction, such as perforin and serine esterases, are found within these granule substructures.
- Cytotoxic mediators are exocytosed in a membrane-enveloped form, not as soluble molecules.
Conclusions:
- The current model of lethal hit delivery requires revision.
- Exocytosed cytotoxic mediators are membrane-enveloped, ensuring directed delivery to target cells.
- The presence of molecules like CD3-T-cell receptor (TCR) complex and CD8 on these membranes facilitates unidirectional delivery of cytotoxic compounds.