Estimation of the rate of killing by cytotoxic T lymphocytes in vivo

Abstract

Cytotoxic T lymphocytes (CTL) help control virus infections by killing virus-infected (target) cells. How fast do CTL find and kill target cells in vivo? Experiments allow us to follow populations of labeled target cells after their transfer into immune mice where they are killed by CTL. Here, we develop models of the migration and killing processes involved in these experiments and use them to quantitatively analyze the in vivo killing data. These models allow us to estimate the rate constant for killing of target cells by CTL.

Fig. 1.

The experimental design of the in vivo CTL killing assays. (A) Control and peptide-pulsed target cells were injected into LCMV immune mice (containing CTL specific to the pulsed target cells). (B) The numbers of control and specific target cells in the spleen are illustrated by the gray and black lines, respectively. The gray line shows how the target cells migrate into the spleen, and the lesser number of specific target cells (black line) shows about how fast these cells are killed by specific CTL. The killing is usually described by the percentage of specific target cells killed [i.e., (1 − target/control) × 100] and is shown by the dashed line.

Fig. 2.

Schematic for the model describing the migration of target cells into the spleen.

Fig. 3.

Migration of unpulsed cells into the spleen. The dots show the individual data points, the dashes are the mean number of cells in the spleen at a given time, and the line shows the best fit of the model described by Eq. 1 to the data.

Fig. 4.

Schematic for the model describing the dynamics of target cells in the spleen. The target cells migrate into the spleen and are killed by CTL.

Fig. 5.

A plot of the estimates for the rate constants for CTL killing, k (min⁻¹) and their 95% CI.