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In silico simulations suggest that Th-cell development is regulated by both selective and instructive mechanisms


Jansson, A and Fagerlind, AM and Karlsson, D and Nilsson, P and Cooley, MA, In silico simulations suggest that Th-cell development is regulated by both selective and instructive mechanisms, Immunology and Cell Biology, 84, (2) pp. 218-226. ISSN 0818-9641 (2006) [Refereed Article]

DOI: doi:10.1111/j.1440-1711.2006.01425.x


Th-cell differentiation is highly influenced by the local cytokine environment. Although cytokines such as IL-12 and IL-4 are known to polarize the Th-cell response towards Th1 or Th2, respectively, it is not known whether these cytokines instruct the developmental fate of uncommitted Th cells or select cells that have already been committed through a stochastic process. We present an individual based model that accommodates both stochastic and deterministic processes to simulate the dynamic behaviour of selective versus instructive Th-cell development. The predictions made by each model show distinct behaviours, which are compared with experimental observations. The simulations show that the instructive model generates an exclusive Th1 or Th2 response in the absence of an external cytokine source, whereas the selective model favours coexistence of the phenotypes. A hybrid model, including both instructive and selective development, shows behaviour similar to either the selective or the instructive model dependent on the strength of activation. The hybrid model shows the closest qualitative agreement with a number of well-established experimental observations. The predictions by each model suggest that neither pure selective nor instructive Th development is likely to be functional as exclusive mechanisms in Th1/Th2 development. © 2006 The Authors.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Cooley, MA (Associate Professor Margaret Cooley)
ID Code:72737
Year Published:2006
Web of Science® Times Cited:4
Deposited By:Medicine
Deposited On:2011-08-31
Last Modified:2012-01-18

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