Intracellular Signaling Networks in the Immune Response: Interleukin-4 introduces Competition and Cooperation to Interleukin-2-Induced T Cell Proliferation
Document Type
Conference Paper
Publication Date
2007
Publication Source
The Journal of Immunology
Abstract
Cells sense and respond to stimuli through signal transduction pathways, which mediate proliferation, differentiation, and survival. The cytokines interleukin-2 (IL-2) and interleukin-4 (IL-4) are key regulators of the immune system, influencing the expansion and differentiation of T cells. Both synergistic and antagonistic effects of IL-2 and -4 co-stimulation have been shown; the antagonism may arise from the sharing of a common receptor subunit. 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/Erk and phosphoinositide (PI) 3-kinase pathways as well as the STAT5 transcription factor. IL-4 is able to activate PI 3-kinase/Akt as well as STAT6, though not Ras/Erk.
We found that IL-4 initially antagonizes, and later synergizes with, IL-2-stimulated HT-2 cell proliferation; a murine T cell line. At a signaling level, IL-4 abates IL-2-stimulated activation levels of Akt, Erk and STAT5 possibly through competition for limiting amounts of common receptor subunit. IL-2/IL-4 co-stimulation provokes prolonged activation only of STAT6. This extended STAT6 activation may be critical in the IL-2/IL-4 induced synergy in T cell growth. Currently, we are investigating the crosstalk between these pathways and their functional roles in IL-2 and IL-4-stimulated T cell responses.
Inclusive pages
B57
ISBN/ISSN
0022-1767
Copyright
Copyright © 2007, American Association of Immunologists
Publisher
American Association of Immunologists
Volume
178
Peer Reviewed
yes
eCommons Citation
Comfort, Kristen K. and Haugh, Jason, "Intracellular Signaling Networks in the Immune Response: Interleukin-4 introduces Competition and Cooperation to Interleukin-2-Induced T Cell Proliferation" (2007). Chemical and Materials Engineering Faculty Publications. 3.
https://ecommons.udayton.edu/cme_fac_pub/3
