Dominance of IL-12 over IL-4 in γδ T cell differentiation leads to default production of IFN-γ: Failure to down-regulate IL-12 receptor β2- chain expression

Zhinan Yin, Dong Hong Zhang, Thomas Welte, Gul Bahtiyar, Sungsoo Jung, Lanzhen Liu, Xin Yuan Fu, Anuradha Ray, Joe Craft

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

γδ T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine γδ T cells acquire the capacity to differentially produce such cytokines. Splenic γδ T cells could be polarized into IFN-γ- or IL-4-secreting cells in vitro; however, in contrast to CD4+ αβ T cells, γδ T cells predominantly produced IFN-γ, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-γ-producing cells expressed the IL-12 receptor β2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed γδ T cells also expressed this receptor, even in the absence of IFN-γ and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed γδ T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-γ by γδ T cells in the presence of IL- 12, despite the availability of IL-4. Early and predominant production of IFN-γ by γδ T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.

Original languageEnglish (US)
Pages (from-to)3056-3064
Number of pages9
JournalJournal of Immunology
Volume164
Issue number6
DOIs
StatePublished - Mar 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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