{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T15:41:31Z","timestamp":1772293291022,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T00:00:00Z","timestamp":1411948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANR grant PrediVac","award":["ANR-12-RPIB-0011"],"award-info":[{"award-number":["ANR-12-RPIB-0011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>CD8 T-cells are critical  in controlling infection by intracellular  pathogens. Upon encountering antigen presenting cells, T-cell receptor activation promotes the differentiation of na\u00efve CD8 T-cells into strongly proliferating  activated and effector stages. We propose a  2D-multiscale computational model to study the maturation of CD8 T-cells in a lymph node controlled by their molecular profile. A novel molecular pathway is presented and converted into an ordinary differential  equation model, coupled with a cellular Potts model to describe cell-cell interactions. Key molecular  players such as activated IL2 receptor and Tbet levels        control the differentiation  from na\u00efve into activated and effector stages, respectively,  while caspases and Fas-Fas ligand interactions control cell apoptosis.  Coupling  this molecular model to the cellular scale successfully  reproduces  qualitatively the evolution of total CD8 T-cell counts observed in mice lymph node, between Day 3 and 5.5 post-infection. Furthermore, this model allows us to make testable predictions  of the evolution of the different CD8 T-cell stages.<\/jats:p>","DOI":"10.3390\/computation2040159","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T11:16:45Z","timestamp":1411989405000},"page":"159-181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study"],"prefix":"10.3390","volume":"2","author":[{"given":"Sotiris","family":"Prokopiou","sequence":"first","affiliation":[{"name":"Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603,  France"}]},{"given":"Loic","family":"Barbarroux","sequence":"additional","affiliation":[{"name":"Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603,  France"},{"name":"Universit\u00e9 Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, F-69622 Villeurbanne-Cedex, France"}]},{"given":"Samuel","family":"Bernard","sequence":"additional","affiliation":[{"name":"Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603,  France"},{"name":"Universit\u00e9 Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, F-69622 Villeurbanne-Cedex, France"}]},{"given":"Julien","family":"Mafille","sequence":"additional","affiliation":[{"name":"Inserm, U1111, Lyon F-69007, France"},{"name":"CNRS, UMR5308, Lyon F-69007, France"},{"name":"Universit\u00e9 Lyon 1, Centre International  de Recherche en Infectiologie, Lyon F-69007, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, Lyon F-69007, France"}]},{"given":"Yann","family":"Leverrier","sequence":"additional","affiliation":[{"name":"Inserm, U1111, Lyon F-69007, France"},{"name":"CNRS, UMR5308, Lyon F-69007, France"},{"name":"Universit\u00e9 Lyon 1, Centre International  de Recherche en Infectiologie, Lyon F-69007, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, Lyon F-69007, France"}]},{"given":"Christophe","family":"Arpin","sequence":"additional","affiliation":[{"name":"Inserm, U1111, Lyon F-69007, France"},{"name":"CNRS, UMR5308, Lyon F-69007, France"},{"name":"Universit\u00e9 Lyon 1, Centre International  de Recherche en Infectiologie, Lyon F-69007, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, Lyon F-69007, France"}]},{"given":"Jacqueline","family":"Marvel","sequence":"additional","affiliation":[{"name":"Inserm, U1111, Lyon F-69007, France"},{"name":"CNRS, UMR5308, Lyon F-69007, France"},{"name":"Universit\u00e9 Lyon 1, Centre International  de Recherche en Infectiologie, Lyon F-69007, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, Lyon F-69007, France"}]},{"given":"Olivier","family":"Gandrillon","sequence":"additional","affiliation":[{"name":"Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603,  France"},{"name":"Universit\u00e9 Lyon 1, Centre de G\u00e9n\u00e9tique et de Physiologie Mol\u00e9culaire  et Cellulaire, F-69622 Villeurbanne-Cedex, France"}]},{"given":"Fabien","family":"Crauste","sequence":"additional","affiliation":[{"name":"Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603,  France"},{"name":"Universit\u00e9 Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, F-69622 Villeurbanne-Cedex, France"}]}],"member":"1968","published-online":{"date-parts":[[2014,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Matheu, M., Teijaro, J., Walsh, K., Greenberg, M., Marsolais, D., Parker, I., Rosen, H., Oldstone, M., and Cahalan, M. 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