Document Type
Dissertation
Publication Date
10-2007
Abstract
Cells sense and respond to chemical and physical stimuli through signal transduction pathways, which mediate cell proliferation, differentiation, migration, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the adaptive immune system, particularly influencing the clonal expansion and differentiation of T cells. At least in culture, both synergistic and antagonistic effects of IL-2 and IL-4 co-stimulation have been reported; the antagonism, when observed, is thought to arise from the utilization of a common subunit shared by IL-2 and IL-4 receptors. We have sought to characterize IL-2 and IL-4 signaling at the level of intracellular pathways activated by these receptors. IL-2 receptors are known to activate the Ras/extracellular signal-regulated kinase (Erk) and phosphoinositide (PI) 3-kinase/Akt pathways as well as the STAT5 transcription factor. IL-4 is unique among cytokines in that it does not activate Ras/Erk; it does activate PI 3-kinase/Akt as well as a distinct STAT, STAT6.
The HT-2 mouse T cell line responds to both IL-2 and IL-4. We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation in a dose-dependent manner. Additionally, transient signaling through the PI3K/Akt and Ras/Erk pathways are required for optimal T cell proliferation. IL-4 stimulates cell adhesion in static cultures, again in a dose-dependent fashion, and it partially inhibits IL-2-stimulated activation of Akt, Erk and STAT5, consistent with a competition effect. IL-2/IL-4 co-stimulation provokes transient activation of Akt, Erk and STAT5 coupled with prolonged activation of STAT6. This signaling profile and the cell adhesion response suggest potential mechanisms by which IL-4 influences the proliferation of helper T cells.
Inclusive pages
1-96
Document Version
Published Version
Copyright
Copyright © 2007, Kristen K. Comfort
Publisher
North Carolina State University
Place of Publication
Raleigh, NC
Peer Reviewed
yes
eCommons Citation
Comfort, Kristen K., "Signaling Pathways Activated by Interleukin-2 and Interluekin-4 Receptors Mediate T Lymphocyte Clonal Expansion" (2007). Chemical and Materials Engineering Faculty Publications. 2.
https://ecommons.udayton.edu/cme_fac_pub/2
Included in
Other Chemical Engineering Commons, Other Materials Science and Engineering Commons, Petroleum Engineering Commons, Polymer and Organic Materials Commons, Thermodynamics Commons
Comments
Document is made available for download with the author's permission. Permission documentation is on file.