Cytotoxic T lymphocyte-mediated cytolysis: an example of programmed cell death in the immune system
Target cells are programmed to die following interaction with cytotoxic T lymphocytes (CTLs). Within minutes of exposure to CTL the target cell's nuclear DNA is fragmented. Target cell lysis, as measured by /sup 51/Cr release, occurs about 60 minutes after induction of DNA fragmentation. DNA fragmentation results from the action of an endonuclease which cleaves DNA in the linker region between nucleosomes. The origin of this nuclease, whether transferred to the target by the CTL or endogenous to the target cell, has not been resolved. DNA fragmentation occurs only when appropriately sensitized CTL are used and is not merely the result of cell death because killing of target cells by extreme deviation from homeostasis, by interruption of energy production, or by lysis with antibody and complement does not induce DNA cleavage. When Triton X-100 is added to target cells which have interacted with CTL, the DNA fragments do not remain in association with the nucleus. This observation suggests that breakdown of overall nuclear structure is induced concomitantly with DNA fragmentation. Morphologically, disruption of nuclear structure and DNA fragmentation are observed as widespread chromatin condensation (apoptosis). Apoptosis is observed in metabolically active target cells and is not a consequence of cell death. A cell whose DNA is extensively fragmented is condemmed to die. Induction of oligonucleosome-sized DNA is also an early event in glucocorticoid-induced thymocyte death and death of T cells upon removal of growth factor. Several similarities exist between these systems and CTL-mediated cytolysis suggesting a final common biochemical pathway for all three types of cell death.
- Research Organization:
- Colorado Univ., Denver (USA). Health Sciences Center
- OSTI ID:
- 6942404
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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DNA
MOLECULAR STRUCTURE
LYMPHOCYTES
CELL KILLING
CHROMIUM 51
DNA-ASE
IMMUNITY
LABELLED COMPOUNDS
RADIO-RELEASE ANALYSIS
TRACER TECHNIQUES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMICAL ANALYSIS
CHROMIUM ISOTOPES
CONNECTIVE TISSUE CELLS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ESTERASES
EVEN-ODD NUCLEI
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
MATERIALS
NUCLEI
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
QUANTITATIVE CHEMICAL ANALYSIS
RADIOISOTOPES
SOMATIC CELLS
550301* - Cytology- Tracer Techniques