Transcriptional Regulation during CD8 T-Cell Immune Responses

Munitić, Ivana; Evaristo, César; Sung, Hsueh Cheng; Rocha, Bénédita

doi:10.1007/978-1-4419-6451-9_2

Cited by 2 publications

(4 citation statements)

References 89 publications

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“…To account for differentiation into memory cells, we introduced the protein Eomes and its interactions with the rest of the network as documented in the literature. Indeed, Eomes is involved in the development of essential properties of memory cells such as survival, lymph node homing capacities or faster response to antigenic stimulation (11, 12, 14).…”

Section: Materials Methods and Modelsmentioning

confidence: 99%

“…Eomes is induced later (11, 61) and its expression is enhanced by the activation of IL2 receptors (7, 13, 56). Eomes promotes the development of new IL2 receptors on cell membrane (14).…”

Section: Materials Methods and Modelsmentioning

confidence: 99%

“…Eomes is not involved in the SLEC vs. MPEC fate choice (12, 13). However, Eomes is necessary for the development of several properties of memory cells [survival, lymph node homing capacities, responsiveness to second infection (11, 12, 14)]. Along the differentiation from effector to memory, the concentration of Tbet in a CD8 T-cell decreases, while the concentration of Eomes increases (11, 15).…”

Section: Introductionmentioning

confidence: 99%

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Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses

et al. 2019

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Activation of naive CD8 T-cells can lead to the generation of multiple effector and memory subsets. Multiple parameters associated with activation conditions are involved in generating this diversity that is associated with heterogeneous molecular contents of activated cells. Although naive cell polarisation upon antigenic stimulation and the resulting asymmetric division are known to be a major source of heterogeneity and cell fate regulation, the consequences of stochastic uneven partitioning of molecular content upon subsequent divisions remain unclear yet. Here we aim at studying the impact of uneven partitioning on molecular-content heterogeneity and then on the immune response dynamics at the cellular level. To do so, we introduce a multiscale mathematical model of the CD8 T-cell immune response in the lymph node. In the model, cells are described as agents evolving and interacting in a 2D environment while a set of differential equations, embedded in each cell, models the regulation of intra and extracellular proteins involved in cell differentiation. Based on the analysis of in silico data at the single cell level, we show that immune response dynamics can be explained by the molecular-content heterogeneity generated by uneven partitioning at cell division. In particular, uneven partitioning acts as a regulator of cell differentiation and induces the emergence of two coexisting sub-populations of cells exhibiting antagonistic fates. We show that the degree of unevenness of molecular partitioning, along all cell divisions, affects the outcome of the immune response and can promote the generation of memory cells.

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Section: Materials Methods and Modelsmentioning

confidence: 99%

“…Eomes is induced later (11, 61) and its expression is enhanced by the activation of IL2 receptors (7, 13, 56). Eomes promotes the development of new IL2 receptors on cell membrane (14).…”

Section: Materials Methods and Modelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses

et al. 2019

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“…Eomes is not involved in the SLEC versus MPEC fate choice [10,11]. However, Eomes is necessary for the development of several properties of memory cells (survival, lymph node homing capacities, responsiveness to second infection [9,10,12]). Along the differentiation from effector to memory, the concentration of Tbet in a CD8 T-cell decreases, while the concentration of Eomes increases [9,13].…”

Section: Introductionmentioning

confidence: 99%

Model-based assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-cell Immune Responses

Girel

Arpin

Marvel

et al. 2018

Preprint

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Activation of naive CD8 T-cells can lead to the generation of multiple effector and memory subsets. Multiple parameters associated with activation conditions are involved in generating this diversity that is associated with heterogeneous molecular contents of activated cells. Naive cell polarisation upon antigenic stimulation and the asymmetric division that results are known to be a major source of heterogeneity and cell fate regulation. The consequences of stochastic uneven partitioning of molecular content upon subsequent divisions remain unclear. Here we aim at studying the impact of uneven partitioning on molecular-content heterogeneity and then on the immune response dynamics at the cellular level. To do so, we introduce a multiscale mathematical model of the CD8 T-cell immune response in the lymph node. In the model, cells are described as agents evolving and interacting in a 2D environment while a set of differential equations, embedded in each cell, models the regulation of intra and extracellular proteins involved in cell differentiation. Based on the analysis of in silico data at the single cell level, we show that immune response dynamics can be explained by the molecular-content heterogeneity generated by

show abstract

Transcriptional Regulation during CD8 T-Cell Immune Responses

Cited by 2 publications

References 89 publications

Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses

Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses

Model-based assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-cell Immune Responses

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