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Rapid changes in target cell lysosomes induced by cytotoxic T cells: indication of target suicide?
A A Pitsillides1, P M Taylor, L Bitensky
1Division of Cellular Biology, Kennedy Institute of Rheumatology, London, GB.
Abstract:
Although many studies have attempted to elucidate how cytotoxic T (Tc) lymphocytes cause the death of target cells, the mechanism is still controversial. In the present study the effect on the integrity of the lysosomes of the target cell has been investigated. We show here that the specific recognition and attachment of cloned type A influenza-specific Tc cells to A/X31 influenza virus-infected target cells caused rapid change in the amount of lysosomal naphthylamidase activity that was bound within the lysosomes, indicating that the lysosomal membranes in the target cells had been totally labilized. Target cells infected with type B influenza virus served as controls. We therefore suggest that the viral specificity of Tc lymphocytes allows for recognition and intimate membrane contact with suitably infected targets. This intimate contact induces sufficient perturbation of the target cell plasma membrane so as to cause total labilization of the target cell lysosomes which could account for intracellular lysis.
Insights
Cytotoxic T lymphocytes induce target cell death by disrupting lysosomal membranes. This labilization of lysosomes leads to intracellular lysis, a key mechanism in cell-mediated immunity.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- The precise mechanism by which cytotoxic T (Tc) lymphocytes induce target cell death remains a subject of ongoing research and debate.
- Understanding this process is crucial for comprehending cell-mediated immunity and developing targeted therapies.
Purpose of the Study:
- To investigate the effect of cytotoxic T lymphocyte interaction on the integrity of target cell lysosomes.
- To determine if lysosomal membrane labilization plays a role in the cytotoxic T lymphocyte-mediated cell death pathway.
Main Methods:
- Utilized cloned type A influenza-specific Tc lymphocytes and A/X31 influenza virus-infected target cells.
- Monitored changes in lysosomal naphthylamidase activity within target cells following Tc cell recognition and attachment.
- Employed type B influenza virus-infected target cells as controls to ensure viral specificity.
Main Results:
- Specific recognition and attachment of influenza-specific Tc cells to infected targets resulted in rapid changes in lysosomal naphthylamidase activity.
- These changes indicated complete labilization of the lysosomal membranes in the target cells.
- Control target cells infected with type B influenza virus did not exhibit the same degree of lysosomal membrane disruption.
Conclusions:
- Viral specificity of Tc lymphocytes facilitates targeted recognition and intimate membrane contact with infected cells.
- This close contact perturbs the target cell's plasma membrane, leading to total labilization of lysosomes.
- Labilization of target cell lysosomes is proposed as a significant mechanism contributing to intracellular lysis during cytotoxic T lymphocyte-mediated killing.