A cellular automata-based mathematical model for thymocyte development

dc.creatorSilva, Hallan Souza e
dc.creatorSavino, Wilson
dc.creatorFeijóo, Raúl A.
dc.creatorVasconcelos, Ana Tereza Ribeiro
dc.date2018-08-21T11:29:25Z
dc.date2018-08-21T11:29:25Z
dc.date2009
dc.date.accessioned2023-09-26T20:09:09Z
dc.date.available2023-09-26T20:09:09Z
dc.identifierSILVA, Hallan Souza e; et al. A Cellular Automata-Based Mathematical Model for Thymocyte Development. Plos One, v.4, n.12, e8233, 12p, Dec. 2009.
dc.identifier1932-6203
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/28247
dc.identifier10.1371/journal.pone.0008233
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849833
dc.descriptionIntrathymic T cell development is an important process necessary for the normal formation of cell-mediated immune responses. Importantly, such a process depends on interactions of developing thymocytes with cellular and extracellular elements of the thymic microenvironment. Additionally, it includes a series of oriented and tunely regulated migration events, ultimately allowing mature cells to cross endothelial barriers and leave the organ. Herein we built a cellular automata-based mathematical model for thymocyte migration and development. The rules comprised in this model take into account the main stages of thymocyte development, two-dimensional sections of the normal thymic microenvironmental network, as well as the chemokines involved in intrathymic cell migration. Parameters of our computer simulations with further adjusted to results derived from previous experimental data using sub-lethally irradiated mice, in which thymus recovery can be evaluated. The model fitted with the increasing numbers of each CD4/CD8-defined thymocyte subset. It was further validated since it fitted with the times of permanence experimentally ascertained in each CD4/CD8-defined differentiation stage. Importantly, correlations using the whole mean volume of young normal adult mice revealed that the numbers of cells generated in silico with the mathematical model fall within the range of total thymocyte numbers seen in these animals. Furthermore, simulations made with a human thymic epithelial network using the same mathematical model generated similar profiles for temporal evolution of thymocyte developmental stages. Lastly, we provided in silico evidence that the thymus architecture is important in the thymocyte development, since changes in the epithelial network result in different theoretical profiles for T cell development/migration. This model likely can be used to predict thymocyte evolution following therapeutic strategies designed for recovery of the thymus in diseases coursing with thymus involution, such as some primary immunodeficiencies, acute infections, and malnutrition.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectModelo matemático
dc.subjectautômatos celulares
dc.subjectDesenvolvimento de timócitos
dc.subjectMathematical Model
dc.subjectCellular Automata
dc.subjectThymocyte Development
dc.titleA cellular automata-based mathematical model for thymocyte development
dc.typeArticle


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