Publication: IL-4-mediated inhibition of IFN-gamma production by CD4+ T cells proceeds by several developmentally regulated mechanisms.

Publié dans: Int Immunol 2004 Mar; 16(3): 501-8

Auteurs: Wurtz O, Bajénoff M, Guerder S

Résumé

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.

Lien vers Pubmed [PMID] – 14978023