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National Academy of Sciences, Proceedings of the National Academy of Sciences, 11(101), p. 3880-3885, 2004

DOI: 10.1073/pnas.0400339101

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Interleukin 2 plays a central role in Th2 differentiation

Journal article published in 2004 by Javier Cote-Sierra, Gilles Foucras ORCID, Liying Guo, Lynda Chiodetti, Howard A. Young, Jane Hu-Li, Jinfang Zhu ORCID, William E. Paul
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Differentiation of naïve CD4 T cells into T helper (Th) 2 cells requires signaling through the T cell receptor and an appropriate cytokine environment. IL-4 is critical for such Th2 differentiation. We show that IL-2 plays a central role in this process. The effect of IL-2 on Th2 generation does not depend on its cell growth or survival effects. Stat5a -/- cells show diminished differentiation to IL-4 production, and forced expression of a constitutively active form of Stat5a replaces the need for IL-2. In vivo IL-2 neutralization inhibits IL-4 production in two models. Studies of restriction enzyme accessibility and binding of Stat5 to chromatin indicate that IL-2 mediates its effect by stabilizing the accessibility of the Il4 gene. Thus, IL-2 plays a critical role in the polarization of naive CD4 T cells to the Th2 phenotype.