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Updated: Aug 26, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
IL-4-mediated inhibition of IFN-gamma production by CD4+ T cells proceeds by several developmentally regulated
Olivier Wurtz1, Marc Bajénoff, Sylvie Guerder
1Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 09, France.
The mechanisms by which Th1 and Th2 cells inter-regulate in vivo are still poorly understood. In this study we examined the plasticity of Th1 cell differentiation and how Th2 cells may down-regulate these responses. We show here that IL-4 affects Th1 cell responses by two developmentally regulated mechanisms. During the commitment phase of naive CD4+ T cells, IL-4 inhibits Th1 cell differentiation and induces a reversion of developing Th1 cells to the Th2 lineage. In contrast, for effector Th1 cells IL-4 does not affect the developmental process, but only the transcription of the IFN-gamma gene. We further show that the difference in IL-4 responsiveness correlates with a loss, in effector Th1 cells, of IL-4-dependent up-regulation of GATA-3 expression despite normal activation of STAT6. Transient inhibition of IFN-gamma production by differentiated effector cells may explain why Th1 and Th2 responses can co-exist in vivo although Th2 effector cells dominate functionally, as observed in some infectious or autoimmune mice models.
The mechanisms by which Th1 and Th2 cells inter-regulate in vivo are still poorly understood. In this study we examined the plasticity of Th1 cell differentiation and how Th2 cells may down-regulate these responses. We show here that IL-4 affects Th1 cell responses by two developmentally regulated mechanisms. During the commitment phase of naive CD4+ T cells, IL-4 inhibits Th1 cell differentiation and induces a reversion of developing Th1 cells to the Th2 lineage. In contrast, for effector Th1 cells IL-4 does not affect the developmental process, but only the transcription of the IFN-gamma gene. We further show that the difference in IL-4 responsiveness correlates with a loss, in effector Th1 cells, of IL-4-dependent up-regulation of GATA-3 expression despite normal activation of STAT6. Transient inhibition of IFN-gamma production by differentiated effector cells may explain why Th1 and Th2 responses can co-exist in vivo although Th2 effector cells dominate functionally, as observed in some infectious or autoimmune mice models.
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