Quantifying Crosstalk Among Interferon-γ, Interleukin-12, and Tumor Necrosis Factor Signaling Pathways Within a TH1 Cell Model

Science Signaling  17 Apr 2012:
Vol. 5, Issue 220, pp. ra32
DOI: 10.1126/scisignal.2002657

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Modeling the T Cell Response

The fate of T cells involved in an immune response is determined in part by the cytokine milieu. Despite our extensive knowledge of the receptors, signaling proteins, and cytokines involved, how downstream signaling pathways interact to determine T cell fate is unclear. Klinke et al. measured receptor abundance, signaling protein activation, cytokine production, and cell population changes and used these parameters to construct mathematical models to gain insights into the signaling pathways in a mouse T cell line that were stimulated by the cytokine interleukin-12 (IL-12). This combined approach uncovered previously unappreciated aspects of IL-12 signaling that determined the T cell response and serves as an example of how mathematical modeling can refine our understanding of signaling pathways.