Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments
| Autor: | Philippe Robert, Stephan Halle, Ananya Rastogi, Michael Meyer-Hermann |
|---|---|
| Přispěvatelé: | BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. |
| Rok vydání: | 2019 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine Cell Apoptosis CD8-Positive T-Lymphocytes Systems Science White Blood Cells 0302 clinical medicine Agent-Based Modeling Animal Cells Medicine and Health Sciences Cytotoxic T cell Biology (General) Cytotoxicity Cell Death Ecology T Cells Chemistry Simulation and Modeling Cell biology In Vivo Imaging medicine.anatomical_structure Computational Theory and Mathematics Cell Processes Modeling and Simulation Physical Sciences Cellular Types Anatomy Preclinical imaging Research Article Computer and Information Sciences Programmed cell death Imaging Techniques QH301-705.5 Immune Cells In silico Immunology Biology Research and Analysis Methods Lymphatic System 03 medical and health sciences Cellular and Molecular Neuroscience In vivo Genetics medicine Humans Molecular Biology Ecology Evolution Behavior and Systematics Photons Blood Cells Biology and Life Sciences Cell Biology Probability Theory Probability Distribution CTL-mediated cytotoxicity CTL 030104 developmental biology Lymph Nodes Mathematics 030215 immunology |
| Zdroj: | e1008428 PLoS computational biology United States PLoS Computational Biology, Vol 16, Iss 12, p e1008428 (2020) PLoS Computational Biology |
| Popis: | In vivo imaging 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-photon in vivo observations. 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 allowing in silico T 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. Author summary Despite having a clear understanding of cytotoxic T lymphocyte (CTL) mediated cytotoxicity mechanisms, its quantitative dynamics remain unexplored at a cellular level. We developed an agent-based model to compare different hypotheses for mechanisms of CTL mediated cytotoxicity that could lead to an increased killing of infected cells at higher interactions with CTLs as seen in vivo. We showed that this behaviour can be explained by modulation of properties by infected cells or CTLs with increasing number of contacts. For the modulation, we compared two modes of signal integration and showed that the number of contacts is the main determinant of cell death. We also studied the impact of contacts between CTLs and apoptotic infected cells on observed killing properties. |
| Databáze: | OpenAIRE |
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