Mechanism of cell-mediated cytotoxicity at the single cell level. VIII. Kinetics of lysis of target cells bound by more than one cytotoxic T lymphocyte
The authors measured the effects of having multiple cytotoxic T lymphycytes (CTL) bound to one target cell by using the single-cell cytotoxicity in the agarose assay. They found that even though there is a variability in the time at which individual target cells are lysed, they can identify a general trend: the mean rate of lysis increases with the number of CTL bound per target cell, reaching a maximum when the CTL-target cell ratio is three. Combining a quantitative model for the rate of lethal hitting in multicellular conjugates with a multi-event model for the rate of target cell disintegration, they developed a new multistage kinetic model for predicting the rate of target cell lysis in multiple lymphocyte-target cell conjugates. The variability in the time at which target cells are hit and the variability in the time until they disintegrate are incorporated into the model. From this analysis, they found that the rate at which a target cell disintegrated after being lethally hit increases with the number of CTL per conjugate. This result is quite surprising, because once the first hit has been received, a target cell can disintegrate in a killer cell-independent manner. Under the conditions of the experiment, it appears as if target cell disintegration is not killer cell-independent. Furthermore, the analysis of the time course of target cell disintegration suggests that the process is not governed by simple first order kinetics, but rather by a more complex multistep mechanism.
- Research Organization:
- Los Alamos National Lab., NM
- OSTI ID:
- 5277913
- Journal Information:
- J. Immunol.; (United States), Vol. 132:5
- Country of Publication:
- United States
- Language:
- English
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