Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments

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Abstract
In vivoimaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs. We developed a three-dimensional agent-based model to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photonin vivoobservations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor. However, when allowingin silicoT cells to initiate new interactions with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with experimental datasets. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided readouts to distinguish CTL killing models.
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Funding Information
  • Helmholtz International Graduate School for Infection Research (VHGS-202)
  • Human Frontier Science Program (RGP0033/2015)
  • Deutsche Forschungsgemeinschaft (158989968 - SFB 900)

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