Title

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

Publisher

American Association of Immunologists

Volume

178

Peer Reviewed

yes