Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study
AbstractCD8 T-cells are critical in controlling infection by intracellular pathogens. Upon encountering antigen presenting cells, T-cell receptor activation promotes the differentiation of naïve 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 naïve 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. View Full-Text
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Prokopiou, S.A.; Barbarroux, L.; Bernard, S.; Mafille, J.; Leverrier, Y.; Arpin, C.; Marvel, J.; Gandrillon, O.; Crauste, F. Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study. Computation 2014, 2, 159-181.
Prokopiou SA, Barbarroux L, Bernard S, Mafille J, Leverrier Y, Arpin C, Marvel J, Gandrillon O, Crauste F. Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study. Computation. 2014; 2(4):159-181.Chicago/Turabian Style
Prokopiou, Sotiris A.; Barbarroux, Loic; Bernard, Samuel; Mafille, Julien; Leverrier, Yann; Arpin, Christophe; Marvel, Jacqueline; Gandrillon, Olivier; Crauste, Fabien. 2014. "Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study." Computation 2, no. 4: 159-181.